RESUMO
Transcription profiles of genes of local immune response were determined in the vagina of women with bacterial vaginosis, aerobic vaginitis, and vulvovaginal candidosis for detection of the most specific immune markers for these vaginal infections. Laboratory diagnosis of the vaginal infections was performed microscopically; the inflammatory reaction in the vagina (leukorrhea) was defined as the presence of >10 white blood cells per field of view. Transcription profiles of IL1b, IL10, IL18, TNFα, TLR4, GATA3, and CD68 were determined using reverse-transcription quantitative real-time PCR. The strongest predictors of aerobic vaginitis were increased levels of IL1b and IL10 mRNA. Bacterial vaginosis was strongly associated with reduced levels of IL18 and GATA3 mRNA. Increased levels of IL1b and TLR4 transcripts showed significant discriminatory power for vulvovaginal candidosis and leukorrhea. The results of this study suggest differential expression of local immune response genes in the vagina of women with different vaginal infections. Detection of specific immune markers in the vagina using reverse-transcriptase PCR could supplement PCR detection of abnormal vaginal microflora for the diagnosis of vaginal infections.
Assuntos
Imunidade Adaptativa/genética , Vagina/imunologia , Vagina/metabolismo , Vaginose Bacteriana/diagnóstico , Adulto , Biomarcadores/análise , Biomarcadores/metabolismo , Candidíase Vulvovaginal/diagnóstico , Candidíase Vulvovaginal/genética , Candidíase Vulvovaginal/imunologia , Candidíase Vulvovaginal/microbiologia , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Vagina/patologia , Vaginose Bacteriana/genética , Vaginose Bacteriana/imunologia , Vaginose Bacteriana/microbiologiaRESUMO
Parkinson's disease (PD) is the second most common neurodegenerative disorder and causes degeneration of dopaminergic neurons in the nigrostriatal system of the brain. PHF10 is one of the most important regulatory subunits of the SWI/SNF chromatin-remodeling protein complex, which controls the gene function and chromatin state in neurons. Two alternative RHF10 isoforms, PHF10-P and PHF10-S, replace each other in the complex to change the target gene pattern. Expression of the PHF10-P and PHF10-S transcripts in the nigrostriatal system and their ratio in blood lymphocytes were found to change in a mouse model of early clinical stage of PD as compared with control mice. Changes in PHF10-S level were also observed in peripheral blood lymphocytes from patients with early clinical stage of PD. A ratio of the PHF10-P and PHF10-S transcripts in peripheral blood cells was assumed to provide a potential marker of early stage PD.
RESUMO
DNA replication begins from multiple sites distributed thoughout the genome and named replication origins. Despite the increasing amount of data on the properties of replication origins, it is still unknown what factors(s) is the primary determinant of ORC localization. Su(Hw) is a zinc-finger protein that is responsible for the activity of the best-studied Drosophila insulators. Here, we show that insulator protein Su(Hw) recruits histone acetyltransferase complex SAGA and chromatin remodeler dSWI/SNF to Su(Hw)-dependent insulators and creates platform for ORC binding. We have found that Su(Hw) is necessary for chromatin remodeling and ORC recruitment regardless of type of surrounding chromatin. Thus, global chromatin state does not influence molecular mechanism underlying ORC positioning in the genome, rather DNA-binding proteins are key determinants that create proper chromatin structure for ORC binding. Su(Hw) is the first example of such a protein.
Assuntos
Cromatina/genética , Proteínas Cromossômicas não Histona/genética , Replicação do DNA , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Genoma de Inseto , Histona Acetiltransferases/genética , Complexo de Reconhecimento de Origem/genética , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Animais , Sítios de Ligação , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , DNA/genética , DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Elementos Facilitadores Genéticos , Histona Acetiltransferases/metabolismo , Elementos Isolantes , Complexo de Reconhecimento de Origem/metabolismo , Origem de Replicação , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Dedos de ZincoRESUMO
For many years, the recruitment of Pol II to promoter region was considered to be the key step in the regulation of transcription. However, Pol II complex was then detected at the promoters of transcriptionally inactive genes. On that kind of genes, transcription regulation is realized by stimulation of promoter bound complex transition into the elongation phase. The available data concerning phenomenon of the transcription regulation by RNA polymerase II pausing mechanism are summarized in the current review. Here we discuss both the detailed mechanism of this process, which was studied in the model of heat shock genes in Drosophila, and some new data obtained from genome-wide studies. Hypotheses concerning functional role of the genes transcriptional regulation by RNA polymerase pausing mechanism are suggested.
Assuntos
Proteínas de Choque Térmico/genética , RNA Polimerase II/genética , Transcrição Gênica , Animais , Regulação da Expressão Gênica , HumanosRESUMO
The role of metazoan coactivator SAYP in nuclear receptor-driven gene activation in the ecdysone cascade of Drosophila is considered. SAYP interacts with DHR3 nuclear receptor and activates the corresponding genes by recruiting the BTFly (Brahma and TFIID) coactivator supercomplex. The knockdown of SAYP leads to a decrease in the level of DHR3-activated transcription. DHR3 and SAYP interact during development and have multiple common targets across the genome.
Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Ecdisona/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Animais , Cromatina/genética , Cromossomos/genética , Proteínas de Drosophila/genética , Ecdisona/genética , Técnicas de Silenciamento de Genes , Redes Reguladoras de Genes , Metamorfose Biológica/genética , Receptores Citoplasmáticos e Nucleares/genética , Fatores de Transcrição/genética , Ativação TranscricionalRESUMO
In the S2 cell system of Drosophila melanogaster a key protein domain mediating the interaction of TFIID and Brahma transcriptional complexes into the BTFly supercomplex has been shown to be an evolutionary conserved SAY domain of the SAYP. TFIID and Brahma coactivators participated in the reporter gene activation induced by the SAY domain in cellular nuclei. The TFIID and Brahma components directly interacting with the SAY domain were identified.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas de Drosophila/metabolismo , Complexos Multiproteicos/metabolismo , Transativadores/metabolismo , Fator de Transcrição TFIID/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica/fisiologia , Animais , Proteínas de Ciclo Celular/genética , Linhagem Celular , Núcleo Celular/genética , Núcleo Celular/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster , Complexos Multiproteicos/genética , Estrutura Terciária de Proteína , Transativadores/genética , Fator de Transcrição TFIID/genética , Fatores de Transcrição/genéticaRESUMO
SAYP is a dual-function transcriptional coactivator of RNA polymerase II. It is a metazoan-specific factor involved in different signaling pathways that control normal development. In Drosophila, SAYP is present in the organism from the early stages of development and participates in cell cycle synchronization at the blastoderm stage. SAYP is abundant in many embryonic cells and in imaginal discs of larvae and is crucial for oogenesis in adults. At the molecular level, SAYP serves as a basis for assembling the BTFly nuclear supercomplex consising of the Brahma and TFIID coactivators. We suppose that BTFly and other similar nuclear supercomplexes play an important role in ontogenesis.
Assuntos
Proteínas de Drosophila/fisiologia , Drosophila/metabolismo , Fatores de Transcrição/fisiologia , Animais , Proteínas de Ciclo Celular/química , Drosophila/embriologia , Drosophila/crescimento & desenvolvimento , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Humanos , Complexos Multiproteicos/química , Mutação , Proteínas de Neoplasias/metabolismo , Especificidade de Órgãos , Transativadores/química , Fator de Transcrição TFIID/química , Fatores de Transcrição/química , Fatores de Transcrição/genética , Dedos de ZincoAssuntos
Dopamina/fisiologia , Lactotrofos/metabolismo , Oxidopamina/farmacologia , Animais , Dopamina/deficiência , Lactotrofos/efeitos dos fármacos , Masculino , Hipófise/efeitos dos fármacos , Prolactina/biossíntese , Prolactina/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Dopamina D2/biossínteseRESUMO
The multisubunit complex which contains the novel evolutionarily conservative transcription factor SAYP was isolated and the protein composition of the complex was determined. It was shown that SAYP unites two complexes with different functions in transcription activation: the chromatin - remodeling complex PBAP (SWI/SNF) and the main component of preinitiation complex of Pol II, general transcription factor TFIID. The isolated super-complex contained the full set of PBAP and TFIID subunits. All components of supercomplex (SAYP, TFIID and PBAP) are essential for its effective interaction with promoters of SAYP-dependent genes.
Assuntos
Montagem e Desmontagem da Cromatina/fisiologia , Proteínas de Drosophila/metabolismo , Complexos Multiproteicos/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica/fisiologia , Animais , Linhagem Celular , Proteínas de Drosophila/genética , Drosophila melanogaster , Complexos Multiproteicos/genética , Regiões Promotoras Genéticas/fisiologia , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Fator de Transcrição TFIID/genética , Fator de Transcrição TFIID/metabolismo , Fatores de Transcrição/genéticaRESUMO
A study was made of the function of the Drosophila melanogaster TRF2 protein. Expression analysis of the trf2(P1) mutation implicated TRF2 in the D. melanogaster embryo development. High-level expression of the trf2 gene was observed in female germline cells. A high level of TRF2 was detected in primary spermatocytes and trophocytes, characterized by intense transcription. In the female gonads, TRF2 was detected in both nurse cells with intense transcription and transcriptionally inactive oocyte nuclei. In addition, TRF2 proved to be necessary for premeiotic chromatin condensation and further differentiation of germline cells.
Assuntos
Proteínas de Drosophila/fisiologia , Drosophila melanogaster/fisiologia , Proteína 2 de Ligação a Repetições Teloméricas/fisiologia , Animais , Diferenciação Celular/fisiologia , Proteínas de Drosophila/genética , Drosophila melanogaster/embriologia , Feminino , Masculino , Mutação , Oócitos/fisiologia , Espermatócitos/fisiologia , Espermatogênese/genética , Espermatogênese/fisiologia , Proteína 2 de Ligação a Repetições Teloméricas/genéticaRESUMO
A biotechnological system for the production of human beta interferon was developed on the basis of a hybrid gene constructed from the coding sequence of the beta interferon gene inserted into the first exon of the sheep beta lactoglobulin gene. It is intended for the expression of human beta interferon in mammary glands of transgenic animals. Two lines of transgenic rabbits were obtained using the hybrid gene. The tissue specificity of the expression of the transgene and the frequency of its inheritance in the first and second generations were studied. The activity of interferon was 2.2 x 10(4)-7.2 x 10(4) IU per milliliter of milk of transgenic female rabbits. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http:// www.maik.ru.
