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1.
Nature ; 608(7922): 275-286, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35948707

RESUMO

The East Antarctic Ice Sheet contains the vast majority of Earth's glacier ice (about 52 metres sea-level equivalent), but is often viewed as less vulnerable to global warming than the West Antarctic or Greenland ice sheets. However, some regions of the East Antarctic Ice Sheet have lost mass over recent decades, prompting the need to re-evaluate its sensitivity to climate change. Here we review the response of the East Antarctic Ice Sheet to past warm periods, synthesize current observations of change and evaluate future projections. Some marine-based catchments that underwent notable mass loss during past warm periods are losing mass at present but most projections indicate increased accumulation across the East Antarctic Ice Sheet over the twenty-first century, keeping the ice sheet broadly in balance. Beyond 2100, high-emissions scenarios generate increased ice discharge and potentially several metres of sea-level rise within just a few centuries, but substantial mass loss could be averted if the Paris Agreement to limit warming below 2 degrees Celsius is satisfied.


Assuntos
Modelos Climáticos , Aquecimento Global , Camada de Gelo , Temperatura , Regiões Antárticas , Previsões , Aquecimento Global/história , Aquecimento Global/prevenção & controle , Aquecimento Global/estatística & dados numéricos , História do Século XXI , Elevação do Nível do Mar/história , Elevação do Nível do Mar/estatística & dados numéricos
2.
Development ; 145(23)2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30389849

RESUMO

Polycomb-group (PcG)-mediated transcriptional repression of target genes can be delineated into two phases. First, following initial repression of target genes by gene-specific transcription factors, PcG proteins recognize the repressed state and assume control of the genes' repression. Second, once the silenced state is established, PcG proteins may maintain repression through an indefinite number of cell cycles. Little is understood about how PcG proteins initially recognize the repressed state of target genes and the steps leading to de novo establishment of PcG-mediated repression. We describe a genetic system in which a Drosophila PcG target gene, giant (gt), is ubiquitously repressed during early embryogenesis by a maternally expressed transcription factor, and show the temporal recruitment of components of three PcG protein complexes: PhoRC, PRC1 and PRC2. We show that de novo PcG recruitment follows a temporal hierarchy in which PhoRC stably localizes at the target gene at least 1 h before stable recruitment of PRC2 and concurrent trimethylation of histone H3 at lysine 27 (H3K27me3). The presence of PRC2 and increased levels of H3K27me3 are found to precede stable binding by PRC1.


Assuntos
Drosophila melanogaster/embriologia , Drosophila melanogaster/metabolismo , Embrião não Mamífero/metabolismo , Proteínas do Grupo Polycomb/metabolismo , Animais , Cromatina/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Elementos Facilitadores Genéticos/genética , Regulação da Expressão Gênica no Desenvolvimento , Histonas/metabolismo , Lisina/metabolismo , Metilação , Modelos Biológicos , Ligação Proteica
3.
Int J Cancer ; 146(3): 839-849, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31001807

RESUMO

Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case-control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), the primary DDT metabolite, and ß-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher ß-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0-3.2; ptrend = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1-3.9; ptrend = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p'-DDE. Our findings provide support for an association between ß-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p'-DDE do not support an association.


Assuntos
Poluentes Ambientais/sangue , Hidrocarbonetos Clorados/sangue , Linfoma não Hodgkin/epidemiologia , Praguicidas/sangue , Idoso , Estudos de Casos e Controles , China/epidemiologia , Poluentes Ambientais/efeitos adversos , Feminino , Seguimentos , Humanos , Hidrocarbonetos Clorados/efeitos adversos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/etiologia , Masculino , Pessoa de Meia-Idade , Praguicidas/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Singapura/epidemiologia
4.
Int J Mol Sci ; 21(7)2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32225118

RESUMO

In this work, we prepared silver nanowires (AgNWs) via the polyol method in the presence or absence of single wall carbon nanotubes (CNTs) and tested their physicochemical, antibacterial and cytotoxic properties. Results showed that the introduction of CNTs lead to the formation of AgNWs at lower temperature, but the final product characteristics of AgNWs and AgNWs-CNT were not significantly different. AgNWs exhibited antibacterial properties against all the studied bacterial species via the formation of oxygen reactive species (ROS) and membrane damage. Furthermore, AgNWs exhibited a dose-dependent and time-dependent toxicity at concentrations ≥ 10 µg/mL. Fibroblasts appeared to be more resistant than human colorectal adenocarcinoma (Caco-2) and osteoblasts to the toxicity of AgNWs. The cytotoxicity of AgNWs was found to be related to the formation of ROS, but not to membrane damage. Overall, these results suggest that AgNWs are potential antibacterial agents against E. coli, S. aureus, MRSA and S. saprophyticus, but their dosage needs to be adjusted according to the route of administration.


Assuntos
Antibacterianos/toxicidade , Nanocompostos/toxicidade , Nanotubos de Carbono/toxicidade , Nanofios/toxicidade , Antibacterianos/química , Células CACO-2 , Membrana Celular/efeitos dos fármacos , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Nanocompostos/química , Nanotubos de Carbono/química , Nanofios/química , Espécies Reativas de Oxigênio/metabolismo , Salmonella/efeitos dos fármacos , Prata/química
5.
Environ Sci Technol ; 53(10): 6018-6024, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31002243

RESUMO

Eleven polybrominated diphenyl ether (tri- to deca-BDE) congeners and 2,2',4,4',5,5'-hexabromobiphenyl (BB153) have been measured in pooled serum samples from the National Health and Nutrition Examination Survey (NHANES) for one decade (from survey years 2005/06 through 2013/14). The pools, which are representative of the general noninstitutionalized population of the United States, encompassed thirty-two demographic groups defined by sex, race/ethnicity (Mexican American, non-Hispanic black, non-Hispanic white, and all other race/ethnicities), and age (12-19, >20-39, >40-59, and ≥60 years). The adjusted geometric means were determined in a multiple linear regression model for the six congeners (BDE28, BDE47, BDE99, BDE100, BDE153, and BB153) with detectable concentrations in at least 60% of pools in each of the thirty-two demographic groups; the level of significance for all statistical comparisons thereof were determined. BDE154 and BDE209 were detected in 60% of the NHANES 2011/12 and 2013/14 pools; only these two survey periods were evaluated for these congeners. The percent change in concentration by a 2-year survey period was calculated. All examined PBDEs reported in five survey periods decreased in concentration, except BDE153, for which concentrations increased by 12.0% (95% CI 7.1-16.4) and 8.4% (95% CI 2.9-14.1) for the age groups 40-59 and ≥60 years, respectively; no significant change was observed in younger age groups. Excluding BDE153, we observed larger percentage decreases by a 2-year survey period for the age groups 12-19, 20-39, and ≥60 years compared with the age group 40-59 years. The percentage decrease by a two-year survey period ranged between -19.6% (BDE99, 20-39 years old) and -4.5% (BDE100, 40-59 years old). Although five polybrominated diphenyl ether (PDBE) congeners and BB153 are still frequently detected in the U.S. general population, PBDE concentrations have decreased since 2005-2006, likely, because of changes in manufacturing practices that started in the mid-2000s.


Assuntos
Éteres Difenil Halogenados , Bifenil Polibromatos , Compostos de Bifenilo , Inquéritos Nutricionais , Estados Unidos
6.
J Oral Maxillofac Surg ; 77(3): 641-647, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30503978

RESUMO

PURPOSE: Buccal squamous cell carcinoma (BSCC) is rare in the United States. Given its location, few anatomic barriers to spread exist and it has been found to have a high locoregional recurrence rate. The role of elective neck dissection (END) in patients with clinically negative neck (N0) is not clear. This study aims to answer the following research question: Among patients with N0 BSCC, does END improve locoregional control rates, distant metastasis rates, and 2- and 5-year survival rates? MATERIALS AND METHODS: A retrospective cohort study was conducted. The sample included patients who received a diagnosis of BSCC. The primary predictor variable was END status (yes or no). Five institutions participated between June 2001 and June 2011: University of Washington, University of Michigan, University of Tennessee, North Memorial Oral and Maxillofacial Surgery in Minnesota, and Head and Neck Surgical Associates (Portland, OR). The primary outcome variable was locoregional recurrence. Secondary outcome variables were distant metastasis and 2- and 5-year survival rates. Other variables collected were demographic characteristics, initial operation, adjuvant therapy, clinical and pathologic data, and staging. Kaplan-Meier and Cox proportional hazards statistics were computed. RESULTS: The sample was composed of 98 patients with clinical N0 BSCC. The mean age was 66 years (range, 30-88 years), and 54% were men. Of the patients, 74 (76%) underwent END. The locoregional recurrence-free rate was 61% for END versus 38% for no END (P = .042). The distant metastasis rate was 4% for END versus 9% for no END. The 2- and 5-year disease-free survival rates were 91% and 75% (P = .042), respectively, for END and 85% and 63% (P = .019), respectively, for no END. CONCLUSIONS: END had a therapeutic effect, as evidenced by a lower locoregional recurrence rate, lower distant metastasis rate, and improved 2- and 5-year survival rates.


Assuntos
Carcinoma de Células Escamosas , Esvaziamento Cervical , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos
7.
Environ Sci Technol ; 52(4): 2287-2294, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29341602

RESUMO

We report longitudinal serum concentrations of select persistent organic pollutants (POPs) in children at ages 7 and 9 years and in their mothers prenatally and again when the children were 9 years old. The participating families were enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal birth cohort study of low-income Hispanic families residing in the Salinas Valley, California. We observed decreasing concentrations in the mothers with year of serum collection (2009 vs 2011) for six out of seven polybrominated diphenyl ether (PBDE) congeners and for 2,2',4,4',5-pentachlorobiphenyl (CB-99; p < 0.05). The 9-year-old children had similarly decreasing serum concentrations of all seven PBDE congeners, CB-99, and 2,2',3,4,4',5'- and 2,3,3',4,4',6-hexachlorobiphenyl (CB-138/158) with year of serum collection (2009 vs 2011; p < 0.05). In mixed effect models accounting for weight gain as the children aged from 7 to 9 years, we observed an annual decrease (-8.3% to -13.4%) in tri- to hexaBDE concentrations (p < 0.001), except for 2,2',3,4,4'-tetrabromodiphenyl ether (BDE-85) and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153). The concentrations of these congeners were not associated with time of serum collection and instead showed an -0.9% to -2.6% decrease per kilogram of weight gain during the study period (p < 0.05). In the case of tetra- to heptachlorobiphenyls, we observed -0.5% to -0.7% decrease in serum concentration per kilogram of weight gain (p < 0.05) and -3.0% to -3.7% decrease in serum concentration per year of aging (p < 0.05), except for 2,3',4,4',5-pentachlorobiphenyl (CB-118) and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), which were not associated with time of serum draw. 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE) decreased -2.4%/kg of weight gain between the two sampling points (p < 0.001). These findings suggest that as children grow, dilution in a larger body size plays an important role in explaining reductions in body burden in the case of traditional POPs such as PCBs and p,p'-DDE. By contrast, in the case of PBDEs, reductions are likely explained by reduction in exposure, as illustrated by decreased concentrations in more recent years, possibly amplified by presumed shorter biological half-life than other POPs.


Assuntos
Poluentes Ambientais , Bifenil Polibromatos , Bifenilos Policlorados , Animais , California , Criança , Estudos de Coortes , Dicloroetilenos , Feminino , Éteres Difenil Halogenados , Humanos , Exposição Materna , Mães
8.
Environ Health ; 14: 23, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25884939

RESUMO

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in many household items. Given concerns over their potential adverse health effects, we identified predictors and evaluated temporal changes of PBDE serum concentrations. METHODS: PBDE serum concentrations were measured in young children (2-8 years old; N = 67), parents of young children (<55 years old; N = 90), and older adults (≥55 years old; N = 59) in California, with concurrent floor wipe samples collected in participants' homes in 2008-2009. We also measured serum concentrations one year later in a subset of children (N = 19) and parents (N = 42). RESULTS: PBDE serum concentrations in children were significantly higher than in adults. Floor wipe concentration is a significant predictor of serum BDE-47, 99, 100 and 154. Positive associations were observed between the intake frequency of canned meat and serum concentrations of BDE-47, 99 and 154, between canned meat entrees and BDE-154 and 209, as well as between tuna and white fish and BDE-153. The model with the floor wipe concentration and food intake frequencies explained up to 40% of the mean square prediction error of some congeners. Lower home values and renting (vs. owning) a home were associated with higher serum concentrations of BDE-47, 99 and 100. Serum concentrations measured one year apart were strongly correlated as expected (r = 0.70-0.97) with a slight decreasing trend. CONCLUSIONS: Floor wipe concentration, food intake frequency, and housing characteristics can explain 12-40% of the prediction error of PBDE serum concentrations. Decreasing temporal trends should be considered when characterizing long-term exposure.


Assuntos
Dieta , Exposição Ambiental , Poluentes Ambientais/sangue , Éteres Difenil Halogenados/sangue , Habitação , Adulto , Idoso , Carga Corporal (Radioterapia) , California , Criança , Pré-Escolar , Monitoramento Ambiental , Poluentes Ambientais/análise , Feminino , Retardadores de Chama/análise , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estações do Ano
9.
Environ Sci Technol ; 48(1): 753-60, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24298999

RESUMO

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and persistent pesticides have been measured in pooled samples representative of the general noninstitutionalized population of the United States. The pools were made from individual sera from the National Health and Nutrition Examination Survey (NHANES) during 2005/06 and 2007/08. The pooled concentrations have been contrasted to NHANES 2003/04 individual measurements to evaluate changes in concentration over time and within survey period differences among age groups, race/ethnicity groups (Mexican American, non-Hispanic Black, non-Hispanic White), and sex. The arithmetic mean serum concentrations of several PCB congeners decreased from NHANES 2003/04 through 2007/08. Larger percentage reductions were seen for younger subjects (12-19 years) compared with older subjects (≥60 years). For example, the arithmetic mean concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) was 36% lower in 12-19 year old adolescents when comparing NHANES 2007/08 with 2003/04; while for subjects over the age of 60 a 14% lower concentration was seen, although, the 95% confidence intervals overlapped. Similarly, the arithmetic mean serum concentrations of tri- to hexaBDEs were lower in NHANES 2007/08 than in 2003/04; however, most confidence intervals of the arithmetic means overlapped. These findings suggest that a reduction in PBDE serum concentrations cannot yet be detected following the discontinuation of pentaBDE in 2004.


Assuntos
Éteres Difenil Halogenados/sangue , Praguicidas/sangue , Bifenilos Policlorados/sangue , Adolescente , Adulto , Negro ou Afro-Americano , Idoso , Criança , Meio Ambiente , Poluentes Ambientais/análise , Feminino , Humanos , Masculino , Americanos Mexicanos , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estados Unidos/etnologia , Adulto Jovem
10.
Nat Struct Mol Biol ; 14(4): 341-3, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17351631

RESUMO

Recent studies have demonstrated that histone methylation can be dynamically regulated through active demethylation. However, no demethylase specific to histone H3 trimethyl-Lys4 (H3K4me3) has been identified. Here we report that the Drosophila melanogaster protein 'little imaginal discs' (Lid), a JmjC domain-containing trithorax group protein, can demethylate H3K4me3. Consistent with its genetic classification, Lid positively regulates Hox gene expression in S2 cells.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/enzimologia , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Lisina/metabolismo , Fatores de Transcrição/metabolismo , Animais , Proteínas de Drosophila/química , Drosophila melanogaster/citologia , Histona Desmetilases , Histona-Lisina N-Metiltransferase/química , Larva/citologia , Metilação , Proteínas Mutantes/metabolismo , Estrutura Terciária de Proteína , Transporte Proteico , RNA Polimerase II/metabolismo , Especificidade por Substrato
11.
Environ Sci Technol ; 46(13): 7373-81, 2012 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-22668079

RESUMO

Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants historically used in textiles, furniture, and electronic products. Recent studies have documented widespread PBDE exposure to humans, with higher levels measured in children than adults. We analyzed 10 tri- to hepta-BDE congener levels in blood collected from 7-year old Mexican-American children living in an agriculture community in California (n = 272). The most frequently detected PBDE congeners in child serum were BDE-47, -99, -100, and -153, all of which were measured in >99% of the children. We used multiple linear regression models to examine associations between child total PBDE levels (ng/g lipid) and determinants of exposure. Factors positively associated with higher PBDE levels in the children were total PBDE levels in maternal serum during pregnancy, duration of exclusive breastfeeding, and having no safe places to play in their neighborhood. Child BMI was inversely associated with serum PBDE levels (regression p-values <0.05). Our findings confirm that exposure to the penta-BDE mixture is ongoing, and that Mexican-American children living in California may be experiencing higher PBDE exposure from their environment compared to children sampled from the general U.S. population. Additional research is needed to assess the health impacts of these exposures.


Assuntos
Índice de Massa Corporal , Exposição Ambiental/análise , Retardadores de Chama/análise , Éteres Difenil Halogenados/sangue , Adolescente , Adulto , Aleitamento Materno , California , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Lactente , Modelos Lineares , Masculino , Exposição Materna/efeitos adversos , Americanos Mexicanos , Modelos Moleculares , Gravidez , Adulto Jovem
12.
Environ Sci Technol ; 45(15): 6553-60, 2011 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-21793581

RESUMO

We measured levels of 10 polybrominated diphenyl ether (PBDE) congeners in serum collected during pregnancy and at delivery from 416 pregnant, predominantly immigrant, women living in Monterey County, CA. The most frequently detected congeners were BDE-47, -99, -100, and -153, all components of the penta mixture, detected in >97% of samples. We used multivariable regression models to examine factors associated with exposure to individual PBDE congeners as well as their total summed concentration (ng/g lipid). Prenatal and delivery total PBDE levels were correlated between sampling times (n = 21; Pearson r = 0.99, p < 0.001). In multivariable models, total PBDE levels increased significantly with time residing in the U.S. (p < 0.001) and among women with ≥3 pieces of stuffed furniture in their homes (p < 0.05). Women's total PBDE levels increased 4.0% (95% CI = 2.8, 5.3) for each additional year residing in the U.S., after adjustment for prepregnancy BMI, weight gain during pregnancy, and SES. Having ≥3 pieces of stuffed furniture in the home was associated with a 26.8% (95% CI = 2.0, 57.5) increase in women's serum PBDE levels. Findings suggest PBDE indoor contamination in California homes is contributing to human exposures in a population of recent immigrants.


Assuntos
Monitoramento Ambiental , Éteres Difenil Halogenados/sangue , Avaliação das Necessidades , Adulto , California , Criança , Estudos de Coortes , Demografia , Dieta , Feminino , Habitação , Humanos , Modelos Lineares , Exposição Materna , Gravidez
13.
Sci Adv ; 7(29)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34272248

RESUMO

Polycomb-group (PcG) proteins are epigenetic regulators that maintain the transcriptional repression of target genes following their initial repression by transcription factors. PcG target genes are repressed in some cells, but active in others. Therefore, a mechanism must exist by which PcG proteins distinguish between the repressed and active states and only assemble repressive chromatin environments at target genes that are repressed. Here, we present experimental evidence that the repressed state of a Drosophila PcG target gene, giant (gt), is not identified by the presence of a repressor. Rather, de novo establishment of PcG-mediated silencing at gt is the default state that is prevented by the presence of an activator or coactivator, which may inhibit the catalytic activity of Polycomb-repressive complex 2 (PRC2).

14.
Nature ; 431(7010): 873-8, 2004 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-15386022

RESUMO

Covalent modification of histones is important in regulating chromatin dynamics and transcription. One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B. Although recent studies have uncovered the enzymes involved in histone H2B ubiquitination and a 'cross-talk' between H2B ubiquitination and histone methylation, the responsible enzymes and the functions of H2A ubiquitination are unknown. Here we report the purification and functional characterization of an E3 ubiquitin ligase complex that is specific for histone H2A. The complex, termed hPRC1L (human Polycomb repressive complex 1-like), is composed of several Polycomb-group proteins including Ring1, Ring2, Bmi1 and HPH2. hPRC1L monoubiquitinates nucleosomal histone H2A at lysine 119. Reducing the expression of Ring2 results in a dramatic decrease in the level of ubiquitinated H2A in HeLa cells. Chromatin immunoprecipitation analysis demonstrated colocalization of dRing with ubiquitinated H2A at the PRE and promoter regions of the Drosophila Ubx gene in wing imaginal discs. Removal of dRing in SL2 tissue culture cells by RNA interference resulted in loss of H2A ubiquitination concomitant with derepression of Ubx. Thus, our studies identify the H2A ubiquitin ligase, and link H2A ubiquitination to Polycomb silencing.


Assuntos
Inativação Gênica , Histonas/metabolismo , Proteínas Repressoras/metabolismo , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina/metabolismo , Sequência de Aminoácidos , Animais , Domínio Catalítico , Linhagem Celular , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/isolamento & purificação , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Células HeLa , Proteínas de Homeodomínio/genética , Humanos , Dados de Sequência Molecular , Complexos Multiproteicos , Proteínas Nucleares/genética , Proteínas Nucleares/isolamento & purificação , Proteínas Nucleares/metabolismo , Nucleossomos/química , Nucleossomos/metabolismo , Complexo Repressor Polycomb 1 , Complexo Repressor Polycomb 2 , Proteínas do Grupo Polycomb , Regiões Promotoras Genéticas/genética , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/isolamento & purificação , Subunidades Proteicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/isolamento & purificação , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/química , Proteínas Repressoras/genética , Proteínas Repressoras/isolamento & purificação , Elementos de Resposta/genética , Fatores de Transcrição/genética , Fatores de Transcrição/isolamento & purificação , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/isolamento & purificação
15.
Nature ; 426(6962): 78-83, 2003 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-14603321

RESUMO

Steroid hormones fulfil important functions in animal development. In Drosophila, ecdysone triggers moulting and metamorphosis through its effects on gene expression. Ecdysone works by binding to a nuclear receptor, EcR, which heterodimerizes with the retinoid X receptor homologue Ultraspiracle. Both partners are required for binding to ligand or DNA. Like most DNA-binding transcription factors, nuclear receptors activate or repress gene expression by recruiting co-regulators, some of which function as chromatin-modifying complexes. For example, p160 class coactivators associate with histone acetyltransferases and arginine histone methyltransferases. The Trithorax-related gene of Drosophila encodes the SET domain protein TRR. Here we report that TRR is a histone methyltransferases capable of trimethylating lysine 4 of histone H3 (H3-K4). trr acts upstream of hedgehog (hh) in progression of the morphogenetic furrow, and is required for retinal differentiation. Mutations in trr interact in eye development with EcR, and EcR and TRR can be co-immunoprecipitated on ecdysone treatment. TRR, EcR and trimethylated H3-K4 are detected at the ecdysone-inducible promoters of hh and BR-C in cultured cells, and H3-K4 trimethylation at these promoters is decreased in embryos lacking a functional copy of trr. We propose that TRR functions as a coactivator of EcR by altering the chromatin structure at ecdysone-responsive promoters.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/efeitos dos fármacos , Drosophila/embriologia , Ecdisona/farmacologia , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Lisina/metabolismo , Animais , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Olho/embriologia , Olho/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Proteínas Hedgehog , Histona-Lisina N-Metiltransferase/genética , Masculino , Metilação/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Ligação Proteica , Receptores de Esteroides/metabolismo
16.
Environ Res ; 110(3): 251-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20129604

RESUMO

BACKGROUND: Levels of brominated flame retardants are increasing in US populations, yet little data are available on body burdens of these and other persistent hormonally active agents (HAAs) in school-aged children. Exposures to such chemicals may affect a number of health outcomes related to development and reproductive function. OBJECTIVE: Determine the distribution of biomarkers of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and organo-chlorinated pesticides (OCPs), such as DDT/DDE, in children, and their variation by key descriptor variables. METHODS: Ethnically diverse cohorts of girls 6-8 y old at baseline are being followed for growth and pubertal development in a multi-site, longitudinal study. Nearly 600 serum samples from the California and Ohio sites were analyzed for lipids, 35 PCB congeners, 11 PBDE congeners, and 9 OCPs. The biomarker distributions were examined and geometric means compared for selected analytes across categories of age, race, site, body mass index (BMI), parental education, maternal age at delivery, and breast feeding in adjusted models. RESULTS: Six PBDE congeners were detected among greater than 70% of samples, with BDE-47 having the highest concentration (median 42.2, range 4.9-855 ng/g lipid). Girls in California had adjusted geometric mean (GM) PBDE levels significantly higher than girls in Ohio. Furthermore, Blacks had significantly higher adjusted GMs of all six PBDE congeners than Whites, and Hispanics had intermediate values. GMs tended to be lower among more obese girls, while other variables were not strongly associated. In contrast, GMs of the six PCB congeners most frequently detected were significantly lower among Blacks and Hispanics than Whites. PCBs and the three pesticides most frequently detected were also consistently lower among girls with high BMI, who were not breast-fed, whose mothers were younger, or whose care-givers (usually parents) were less educated. Girls in California had higher GMs than in Ohio for the pesticides and most PCB congeners, but the opposite for CB-99 and -118. CONCLUSIONS: Several of these potential HAAs were detected in nearly all of these young girls, some at relatively high levels, with variation by geographic location and other demographic factors that may reflect exposure pathways. The higher PBDE levels in California likely reflect differences in fire regulation and safety codes, with potential policy implications.


Assuntos
Poluentes Ambientais/sangue , Retardadores de Chama/metabolismo , Éteres Difenil Halogenados/sangue , Hidrocarbonetos Clorados/sangue , Praguicidas/sangue , Bifenilos Policlorados/sangue , Carga Corporal (Radioterapia) , California , Criança , DDT/sangue , Diclorodifenil Dicloroetileno/sangue , Monitoramento Ambiental , Feminino , Humanos , Ohio , Estados Unidos
17.
Genetics ; 214(3): 623-634, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31919108

RESUMO

Polycomb-group (PcG) proteins are evolutionarily conserved epigenetic regulators whose primary function is to maintain the transcriptional repression of target genes. Recruitment of Drosophila melanogaster PcG proteins to target genes requires the presence of one or more Polycomb Response Elements (PREs). The functions or necessity for more than one PRE at a gene are not clear and individual PREs at some loci may have distinct regulatory roles. Various combinations of sequence-specific DNA-binding proteins are present at a given PRE, but only Pleiohomeotic (Pho) is present at all strong PREs. The giant (gt) locus has two PREs, a proximal PRE1 and a distal PRE2. During early embryonic development, Pho binds to PRE1 ∼30-min prior to stable binding to PRE2. This observation indicated a possible dependence of PRE2 on PRE1 for PcG recruitment; however, we find here that PRE2 recruits PcG proteins and maintains transcriptional repression independently of Pho binding to PRE1. Pho-like (Phol) is partially redundant with Pho during larval development and binds to the same DNA sequences in vitro Although binding of Pho to PRE1 is dependent on the presence of consensus Pho-Phol-binding sites, Phol binding is less so and appears to play a minimal role in recruiting other PcG proteins to gt Another PRE-binding protein, Sp1/Kruppel-like factor, is dependent on the presence of Pho for PRE1 binding. Further, we show that, in addition to silencing gene expression, PcG proteins dampen transcription of an active gene.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Proteínas do Grupo Polycomb/genética , Elementos de Resposta/genética , Fator de Transcrição Sp1/genética , Animais , Sítios de Ligação/genética , Cromatina/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Inativação Gênica , Ligação Proteica/genética
18.
Mol Cell Biol ; 26(7): 2637-47, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16537908

RESUMO

The Extra sex combs (ESC) protein is a Polycomb group (PcG) repressor that is a key noncatalytic subunit in the ESC-Enhancer of zeste [E(Z)] histone methyltransferase complex. Survival of esc homozygotes to adulthood based solely on maternal product and peak ESC expression during embryonic stages indicate that ESC is most critical during early development. In contrast, two other PcG repressors in the same complex, E(Z) and Suppressor of zeste-12 [SU(Z)12], are required throughout development for viability and Hox gene repression. Here we describe a novel fly PcG repressor, called ESC-Like (ESCL), whose biochemical, molecular, and genetic properties can explain the long-standing paradox of ESC dispensability during postembryonic times. Developmental Western blots show that ESCL, which is 60% identical to ESC, is expressed with peak abundance during postembryonic stages. Recombinant complexes containing ESCL in place of ESC can methylate histone H3 with activity levels, and lysine specificity for K27, similar to that of the ESC-containing complex. Coimmunoprecipitations show that ESCL associates with E(Z) in postembryonic cells and chromatin immunoprecipitations show that ESCL tracks closely with E(Z) on Ubx regulatory DNA in wing discs. Furthermore, reduced escl+ dosage enhances esc loss-of-function phenotypes and double RNA interference knockdown of ESC/ESCL in wing disc-derived cells causes Ubx derepression. These results suggest that ESCL and ESC have similar functions in E(Z) methyltransferase complexes but are differentially deployed as development proceeds.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/crescimento & desenvolvimento , Drosophila/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Histona-Lisina N-Metiltransferase/metabolismo , Sequência de Aminoácidos , Animais , Cromatina/genética , Cromatina/metabolismo , Drosophila/citologia , Drosophila/enzimologia , Perfilação da Expressão Gênica , Melhoramento Genético , Histona Metiltransferases , Proteínas de Homeodomínio/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Complexo Repressor Polycomb 1 , Complexo Repressor Polycomb 2 , Ligação Proteica , Proteínas Metiltransferases , Subunidades Proteicas/metabolismo , Sequências Reguladoras de Ácido Nucleico/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Asas de Animais/metabolismo
20.
Chemosphere ; 73(1 Suppl): S131-6, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18501952

RESUMO

Seven polybrominated diphenyl ether (PBDE) congeners were measured in the particulate fraction (<2mm) of household dust samples (n=40), collected in four different countries (Australia, Germany, Great Britain, and United States). Dust samples from Germany contained the lowest concentrations of total PBDEs (median: 74 ng/g, range: 17-550 ng/g dust). Australian dust contained the second lowest concentration (median: 1200 ng/g, range: 500-13,000 ng/g dust). The dust from the United States and Great Britain contained the highest measured amounts of total PBDEs (US median: 4200 ng/g dust, range: 520-29,000 ng/g; Great Britain median: 10,000 ng/g, range: 950-54,000 ng/g). Daily intake of PBDEs has been estimated from published reference values on daily dust intake rates. The highest daily intake of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) found was in the United States (<1-330 ng/day) and the lowest was in Germany (<1-2 ng/day). The PBDE congeners present in commercially available pentabromodiphenyl ether were the highest in concentration in the United States, and the congener distribution was similar to that of the technical preparation (i.e., 2,2',4,4',5-pentabromodiphenyl ether [BDE-99] was similar in concentration to that of BDE-47). We conclude that further studies are required to investigate human indoor exposure to PBDEs across countries and to determine the risk factors related to indoor design factors.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Poeira/análise , Habitação , Éteres Fenílicos/análise , Bifenil Polibromatos/análise , Europa (Continente) , Éteres Difenil Halogenados , Éteres Fenílicos/química , Bifenil Polibromatos/química , Estados Unidos
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