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1.
Nat Immunol ; 24(9): 1552-1564, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37524800

RESUMO

The nuclear factor kappa B (NF-κB) family of transcription factors orchestrates signal-induced gene expression in diverse cell types. Cellular responses to NF-κB activation are regulated at the level of cell and signal specificity, as well as differential use of family members (subunit specificity). Here we used time-dependent multi-omics to investigate the selective functions of Rel and RelA, two closely related NF-κB proteins, in primary B lymphocytes activated via the B cell receptor. Despite large numbers of shared binding sites genome wide, Rel and RelA directed kinetically distinct cascades of gene expression in activated B cells. Single-cell RNA sequencing revealed marked heterogeneity of Rel- and RelA-specific responses, and sequential binding of these factors was not a major mechanism of protracted transcription. Moreover, nuclear co-expression of Rel and RelA led to functional antagonism between the factors. By rigorously identifying the target genes of each NF-κB subunit, these studies provide insights into exclusive functions of Rel and RelA in immunity and cancer.


Assuntos
NF-kappa B , Fator de Transcrição RelA , NF-kappa B/metabolismo , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Linfócitos B/metabolismo , Sítios de Ligação , Receptores de Antígenos/metabolismo
2.
Immunity ; 55(6): 1051-1066.e4, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35649416

RESUMO

Microbial exposures are crucial environmental factors that impact healthspan by sculpting the immune system and microbiota. Antibody profiling via Phage ImmunoPrecipitation Sequencing (PhIP-Seq) provides a high-throughput, cost-effective approach for detecting exposure and response to microbial protein products. We designed and constructed a library of 95,601 56-amino acid peptide tiles spanning 14,430 proteins with "toxin" or "virulence factor" keyword annotations. We used PhIP-Seq to profile the antibodies of ∼1,000 individuals against this "ToxScan" library. In addition to enumerating immunodominant antibody epitopes, we studied the age-dependent stability of the ToxScan profile and used a genome-wide association study to find that the MHC-II locus modulates bacterial epitope selection. We detected previously described anti-flagellin antibody responses in a Crohn's disease cohort and identified an association between anti-flagellin antibodies and juvenile dermatomyositis. PhIP-Seq with the ToxScan library is thus an effective tool for studying the environmental determinants of health and disease at cohort scale.


Assuntos
Bacteriófagos , Biblioteca de Peptídeos , Sequência de Aminoácidos , Anticorpos , Formação de Anticorpos , Bacteriófagos/genética , Estudo de Associação Genômica Ampla , Humanos , Epitopos Imunodominantes , Prevalência , Fatores de Virulência/genética
3.
Immunity ; 54(11): 2465-2480.e5, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34706222

RESUMO

Epigenetic reprogramming underlies specification of immune cell lineages, but patterns that uniquely define immune cell types and the mechanisms by which they are established remain unclear. Here, we identified lineage-specific DNA methylation signatures of six immune cell types from human peripheral blood and determined their relationship to other epigenetic and transcriptomic patterns. Sites of lineage-specific hypomethylation were associated with distinct combinations of transcription factors in each cell type. By contrast, sites of lineage-specific hypermethylation were restricted mostly to adaptive immune cells. PU.1 binding sites were associated with lineage-specific hypo- and hypermethylation in different cell types, suggesting that it regulates DNA methylation in a context-dependent manner. These observations indicate that innate and adaptive immune lineages are specified by distinct epigenetic mechanisms via combinatorial and context-dependent use of key transcription factors. The cell-specific epigenomics and transcriptional patterns identified serve as a foundation for future studies on immune dysregulation in diseases and aging.


Assuntos
Metilação de DNA , Epigênese Genética , Epigenômica , Regulação da Expressão Gênica , Imunidade , Fatores de Transcrição/metabolismo , Transcriptoma , Epigenômica/métodos , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Fatores de Transcrição/genética
4.
Cell ; 153(6): 1281-95, 2013 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-23706625

RESUMO

Understanding the topological configurations of chromatin may reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here, we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3D interactions that undergo marked reorganization at the submegabase scale during differentiation. Distinct combinations of CCCTC-binding factor (CTCF), Mediator, and cohesin show widespread enrichment in chromatin interactions at different length scales. CTCF/cohesin anchor long-range constitutive interactions that might form the topological basis for invariant subdomains. Conversely, Mediator/cohesin bridge short-range enhancer-promoter interactions within and between larger subdomains. Knockdown of Smc1 or Med12 in embryonic stem cells results in disruption of spatial architecture and downregulation of genes found in cohesin-mediated interactions. We conclude that cell-type-specific chromatin organization occurs at the submegabase scale and that architectural proteins shape the genome in hierarchical length scales.


Assuntos
Linhagem da Célula , Cromatina/metabolismo , Genoma , Proteínas Nucleares/análise , Animais , Fator de Ligação a CCCTC , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Células-Tronco Embrionárias/química , Células-Tronco Embrionárias/metabolismo , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Estudo de Associação Genômica Ampla , Complexo Mediador/genética , Complexo Mediador/metabolismo , Camundongos , Células-Tronco Neurais/química , Células-Tronco Neurais/metabolismo , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas , Proteínas Repressoras/metabolismo , Análise de Sequência de DNA , Coesinas
5.
Nat Immunol ; 21(10): 1146-1151, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32855555

Assuntos
Angioedema/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Citocinas/metabolismo , Pneumonia Viral/imunologia , Angioedema/sangue , Angioedema/patologia , Angioedema/virologia , Enzima de Conversão de Angiotensina 2 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Biomarcadores/sangue , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Congressos como Assunto , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/virologia , Citocinas/antagonistas & inibidores , Citocinas/sangue , Citocinas/imunologia , Humanos , Internet , Sistema Calicreína-Cinina/efeitos dos fármacos , Sistema Calicreína-Cinina/imunologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Alvéolos Pulmonares/imunologia , Alvéolos Pulmonares/patologia , SARS-CoV-2 , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Fatores de Tempo , Tempo para o Tratamento , Tratamento Farmacológico da COVID-19
6.
Cell ; 150(2): 241-3, 2012 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-22817885

RESUMO

A systematic analysis of LPS-induced gene expression in macrophages by Bhatt et al. demonstrates that inflammatory responses are governed primarily at the level of transcription initiation. Unexpectedly, full-length nascent RNAs that contain introns appear to accumulate on chromatin, presumably to complete processing, prior to release of functional mRNA for export to the cytoplasm.

8.
Cell ; 147(2): 332-43, 2011 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-21982154

RESUMO

The immunoglobulin heavy-chain (IgH) gene locus undergoes radial repositioning within the nucleus and locus contraction in preparation for gene recombination. We demonstrate that IgH locus conformation involves two levels of chromosomal compaction. At the first level, the locus folds into several multilooped domains. One such domain at the 3' end of the locus requires an enhancer, Eµ; two other domains at the 5' end are Eµ independent. At the second level, these domains are brought into spatial proximity by Eµ-dependent interactions with specific sites within the V(H) region. Eµ is also required for radial repositioning of IgH alleles, indicating its essential role in large-scale chromosomal movements in developing lymphocytes. Our observations provide a comprehensive view of the conformation of IgH alleles in pro-B cells and the mechanisms by which it is established.


Assuntos
Linfócitos B/metabolismo , Núcleo Celular/genética , Cromatina/química , Genes de Cadeia Pesada de Imunoglobulina , Cadeias Pesadas de Imunoglobulinas/genética , Animais , Fator de Ligação a CCCTC , Elementos Facilitadores Genéticos , Região Variável de Imunoglobulina , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Proteínas Repressoras/metabolismo , Recombinação V(D)J , Fator de Transcrição YY1/metabolismo
9.
Mol Cell ; 70(1): 21-33.e6, 2018 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-29576529

RESUMO

Immunoglobulin heavy-chain (IgH) genes are assembled by DNA rearrangements that juxtapose a variable (VH), a diversity (DH), and a joining (JH) gene segment. Here, we report that in the absence of intergenic control region 1 (IGCR1), the intronic enhancer (Eµ) associates with the next available CTCF binding site located close to VH81X via putative heterotypic interactions involving YY1 and CTCF. The alternate Eµ/VH81X loop leads to formation of a distorted recombination center and altered DH rearrangements and disrupts chromosome conformation that favors distal VH recombination. Cumulatively, these features drive highly skewed, Eµ-dependent recombination of VH81X. Sequential deletion of CTCF binding regions on IGCR1-deleted alleles suggests that they influence recombination of single proximal VH gene segments. Our observations demonstrate that Eµ interacts differently with IGCR1- or VH-associated CTCF binding sites and thereby identify distinct roles for insulator-like elements in directing enhancer activity.


Assuntos
Montagem e Desmontagem da Cromatina , DNA Intergênico/genética , Elementos Facilitadores Genéticos , Genes de Cadeia Pesada de Imunoglobulina , Loci Gênicos , Região Variável de Imunoglobulina/genética , Células Precursoras de Linfócitos B/metabolismo , Recombinação Genética , Animais , Sítios de Ligação , Fator de Ligação a CCCTC/genética , Fator de Ligação a CCCTC/metabolismo , Linhagem Celular , DNA Intergênico/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Região Variável de Imunoglobulina/imunologia , Região Variável de Imunoglobulina/metabolismo , Camundongos da Linhagem 129 , Camundongos Knockout , Conformação de Ácido Nucleico , Células Precursoras de Linfócitos B/imunologia , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
10.
Immunity ; 44(3): 516-518, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26982358

RESUMO

In this issue of Immunity, Boller et al. (2016) show that a C-terminal domain of EBF1 is required for chromatin binding and induction of DNase I hypersensitive sites. These properties mark EBF1 as a pioneer factor in B cell development and demonstrate a role for non-DNA binding domains in this process.


Assuntos
Linfócitos B/fisiologia , Cromatina/metabolismo , Células Progenitoras Linfoides/fisiologia , Transativadores/metabolismo , Animais
11.
Proc Natl Acad Sci U S A ; 119(18): e2115567119, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35476510

RESUMO

B and T lymphocytes of the adaptive immune system undergo proliferative bursts to generate pools of antigen-specific cells for effective immunity. Here we show that in contrast to the canonical view that G1 progression signals are essential after mitosis to reenter S phase, B lymphocytes sustain several rounds of mitogen-independent cell division following the first mitosis. Such division appears to be driven by unique characteristics of the postmitotic G1 phase that has features of S and G2/M phases. Birc5 (survivin), a protein associated with chromosome segregation in G2/M, is expressed in the G1 phase of divided B cells and is necessary for mitogen-independent divisions. The partially active G1 phase and propensity for apoptosis inherited after each division may underlie rapid proliferation and cell death, which are hallmarks of B cell proliferative responses.


Assuntos
Mitógenos , Proteômica , Linfócitos B , Divisão Celular , Fase G1 , Peptídeos e Proteínas de Sinalização Intercelular , Survivina/genética
12.
J Biol Chem ; 299(12): 105373, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37865318

RESUMO

The bacteriophage capsid protein, Psu (polarity suppression), inhibits the bacterial transcription terminator, Rho. In an effort to find nontraditional antibacterial agents, we previously designed peptides from the Psu C terminus that function as inhibitors of Rho. Here, we demonstrated that these peptides have positive surface-charge densities, and they downregulate many genes in Escherichia coli. We hypothesized that these peptides could bind to nucleic acids and repress gene expression. One of these peptides, peptide 33, represses in vitro transcription from the T7A1 and Plac promoters efficiently by blocking the access of RNA polymerase to the promoter, a mode of transcription repression akin to many bacterial repressors. In vivo, expressions of the peptides reduce the total RNA level as well as transcription from Plac and Posm promoters significantly. However, they are less efficient in repressing transcription from the rRNA promoters with a very high turnover of RNA polymerase. The peptide 33 binds to both single and dsDNA as well as to RNA with dissociation constants ranging from 1 to 5 µM exhibiting preferences for the single-stranded DNA and RNAs. These interactions are salt-resistant and not sequence-specific. Interactions with dsDNA are entropy-driven, while it is enthalpy-driven for the ssDNA. This mode of interaction with nucleic acids is similar to many nonspecific ssDNA-binding proteins. Expression of peptide 33 induces cell elongation and impaired cell division, possibly due to the dislodging of the DNA-binding proteins. Overall, we surmised that these synthetic transcription repressors would function like bacterial nucleoid-associated proteins.


Assuntos
Bacteriófagos , Ácidos Nucleicos , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Bacteriófagos/metabolismo , Transcrição Gênica , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Bactérias/metabolismo , Peptídeos/metabolismo , RNA/metabolismo
13.
Nat Immunol ; 13(12): 1205-12, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23104096

RESUMO

Genes encoding immunoglobulin heavy chains (Igh) are assembled by rearrangement of variable (V(H)), diversity (D(H)) and joining (J(H)) gene segments. Three critical constraints govern V(H) recombination. These include timing (V(H) recombination follows D(H) recombination), precision (V(H) gene segments recombine only to DJ(H) junctions) and allele specificity (V(H) recombination is restricted to DJ(H)-recombined alleles). Here we provide a model for these universal features of V(H) recombination. Analyses of DJ(H)-recombined alleles showed that DJ(H) junctions were selectively epigenetically marked, became nuclease sensitive and bound RAG recombinase proteins, which thereby permitted D(H)-associated recombination signal sequences to initiate the second step of Igh gene assembly. We propose that V(H) recombination is precise, because these changes did not extend to germline D(H) segments located 5' of the DJ(H) junction.


Assuntos
Linfócitos B/metabolismo , Epigênese Genética , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Genes de Cadeia Pesada de Imunoglobulina , Cadeias Pesadas de Imunoglobulinas/genética , Região de Junção de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Animais , Linhagem Celular , Cromatina/metabolismo , Histonas/metabolismo , Camundongos , Células Precursoras de Linfócitos B/imunologia , Células Precursoras de Linfócitos B/metabolismo , Recombinases/metabolismo , Recombinação Genética
14.
Genes Dev ; 30(8): 873-5, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-27083993

RESUMO

Generation of a diverse repertoire of antigen receptor specificities via DNA recombination underpins adaptive immunity. In this issue ofGenes&Development, Carmona and colleagues (pp. 909-917) provide novel insights into the origin and function of recombination-activating gene 1 (RAG1) and RAG2, the lymphocyte-specific components of the recombinase involved in the process.


Assuntos
Imunidade Adaptativa/fisiologia , Imunidade Adaptativa/genética , Imunidade Adaptativa/imunologia , Animais , Proteínas de Ligação a DNA/imunologia , Proteínas de Homeodomínio/imunologia , Humanos , VDJ Recombinases/genética , VDJ Recombinases/metabolismo
15.
J Biol Chem ; 298(6): 102001, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35500654

RESUMO

Bacterial Rho is a RNA-dependent ATPase that functions in the termination of transcription. The in vivo nature of the bacterial Rho-dependent terminators, as well as the mechanism of the Rho-dependent termination process, are not fully understood. Here, we measured the in vivo termination efficiencies of 72 Rho-dependent terminators in Escherichia coli by systematically performing qRT-PCR analyses of cDNA prepared from mid-log phase bacterial cultures. We found that these terminators exhibited a wide range of efficiencies, and many behaved differently in vivo compared to the predicted or experimentally determined efficiencies in vitro. Rho-utilization sites (rut sites) present in the RNA terminator sequences are characterized by the presence of C-rich/G-poor sequences or C > G bubbles. We found that weaker terminators exhibited a robust correlation with the properties (size, length, density, etc.) of these C > G bubbles of their respective rut sites, while stronger terminators lack this correlation, suggesting a limited role of rut sequences in controlling in vivo termination efficiencies. We also found that in vivo termination efficiencies are dependent on the rates of ATP hydrolysis as well as Rho-translocation on the nascent RNA. We demonstrate that weaker terminators, in addition to having rut sites with diminished C > G bubble sizes, are dependent on the Rho-auxiliary factor, NusG, in vivo. From these results, we concluded that in vivo Rho-dependent termination follows a nascent RNA-dependent pathway, where Rho-translocation along the RNA is essential and rut sequences may recruit Rho in vivo, but Rho-rut binding strengths do not regulate termination efficiencies.


Assuntos
Proteínas de Escherichia coli , RNA Bacteriano , Fator Rho , Transcrição Gênica , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , RNA Bacteriano/metabolismo , Fator Rho/genética , Fator Rho/metabolismo , Regiões Terminadoras Genéticas , Fatores de Transcrição/metabolismo
16.
Genes Dev ; 29(16): 1683-95, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26302788

RESUMO

Conformation of antigen receptor gene loci spatially juxtaposes rearranging gene segments in the appropriate cell lineage and developmental stage. We describe a three-step pathway that establishes the structure of the 2.8-Mb immunoglobulin heavy chain gene (IgH) locus in pro-B cells. Each step uses a different transcription factor and leads to increasing levels of structural organization. CTCF mediates one level of compaction that folds the locus into several 250- to 400-kb subdomains, and Pax5 further compacts the 2-Mb region that encodes variable (VH) gene segments. The 5' and 3' domains are brought together by the transcription factor YY1 to establish the configuration within which gene recombination initiates. Such stepwise mechanisms may apply more generally to establish regulatory fine structure within megabase-sized topologically associated domains.


Assuntos
Cadeias Pesadas de Imunoglobulinas/química , Cadeias Pesadas de Imunoglobulinas/genética , Células Precursoras de Linfócitos B/química , Animais , Fator de Ligação a CCCTC , Células Cultivadas , Hibridização in Situ Fluorescente , Camundongos Endogâmicos C57BL , Fator de Transcrição PAX5/genética , Fator de Transcrição PAX5/metabolismo , Conformação Proteica , Dobramento de Proteína , Estrutura Terciária de Proteína , Recombinação Genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , alfa-Amilases Salivares/metabolismo , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
17.
J Biol Chem ; 296: 100653, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33845047

RESUMO

The transcription terminator Rho regulates many physiological processes in bacteria, such as antibiotic sensitivity, DNA repair, RNA remodeling, and so forth, and hence, is a potential antimicrobial target, which is unexplored. The bacteriophage P4 capsid protein, Psu, moonlights as a natural Rho antagonist. Here, we report the design of novel peptides based on the C-terminal region of Psu using phenotypic screening methods. The resultant 38-mer peptides, in addition to containing mutagenized Psu sequences, also contained plasmid sequences, fused to their C termini. Expression of these peptides inhibited the growth of Escherichia coli and specifically inhibited Rho-dependent termination in vivo. Peptides 16 and 33 exhibited the best Rho-inhibitory properties in vivo. Direct high-affinity binding of these two peptides to Rho also inhibited the latter's RNA-dependent ATPase and transcription termination functions in vitro. These two peptides remained functional even if eight to ten amino acids were deleted from their C termini. In silico modeling and genetic and biochemical evidence revealed that these two peptides bind to the primary RNA-binding site of the Rho hexamer near its subunit interfaces. In addition, the gene expression profiles of these peptides and Psu overlapped significantly. These peptides also inhibited the growth of Mycobacteria and inhibited the activities of Rho proteins from Mycobacterium tuberculosis, Xanthomonas, Vibrio cholerae, and Salmonella enterica. Our results showed that these novel anti-Rho peptides mimic the Rho-inhibition function of the ∼42-kDa dimeric bacteriophage P4 capsid protein, Psu. We conclude that these peptides and their C-terminal deletion derivatives could provide a basis on which to design novel antimicrobial peptides.


Assuntos
Proteínas do Capsídeo/farmacologia , Desenho de Fármacos , Proteínas de Escherichia coli/antagonistas & inibidores , Escherichia coli/metabolismo , Mycobacterium tuberculosis/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Regiões Terminadoras Genéticas , Xanthomonas/efeitos dos fármacos , Sequência de Aminoácidos , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Mycobacterium tuberculosis/crescimento & desenvolvimento , Biblioteca de Peptídeos , Plasmídeos , Ligação Proteica , Homologia de Sequência , Xanthomonas/crescimento & desenvolvimento
18.
Annu Rev Microbiol ; 71: 687-709, 2017 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-28731845

RESUMO

At the end of the multistep transcription process, the elongating RNA polymerase (RNAP) is dislodged from the DNA template either at specific DNA sequences, called the terminators, or by a nascent RNA-dependent helicase, Rho. In Escherichia coli, about half of the transcription events are terminated by the Rho protein. Rho utilizes its RNA-dependent ATPase activities to translocate along the mRNA and eventually dislodges the RNAP via an unknown mechanism. The transcription elongation factor NusG facilitates this termination process by directly interacting with Rho. In this review, we discuss current models describing the mechanism of action of this hexameric transcription terminator, its regulation by different cis and trans factors, and the effects of the termination process on physiological processes in bacterial cells, particularly E. coli and Salmonella enterica Typhimurium.


Assuntos
Escherichia coli/enzimologia , Escherichia coli/genética , Fator Rho/metabolismo , Salmonella typhimurium/enzimologia , Salmonella typhimurium/genética , Terminação da Transcrição Genética
19.
Opt Lett ; 47(1): 46-49, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34951879

RESUMO

We present a spatiotemporally mode-locked Mamyshev oscillator. A wide variety of multimode mode-locked states, with varying degrees of spatiotemporal coupling, are observed. We find that some control of the modal content of the output beam is possible through the cavity design. Comparison of simulations with experiments indicates that spatiotemporal mode locking (STML) is enabled by nonlinear intermodal interactions and spatial filtering, along with the Mamyshev mechanism. This work represents a first, to the best of our knowledge, exploration of STML in an oscillator with a Mamyshev saturable absorber.

20.
Eur J Immunol ; 50(6): 822-838, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32092784

RESUMO

Immunoglobulin class switch recombination (CSR) occurs in activated B cells with increased mitochondrial mass and membrane potential. Transcription factor Yin Yang 1 (YY1) is critical for CSR and for formation of the DNA loops involved in this process. We therefore sought to determine if YY1 knockout impacts mitochondrial gene expression and mitochondrial function in murine splenic B cells, providing a potential mechanism for regulating CSR. We identified numerous genes in splenic B cells differentially regulated when cells are induced to undergo CSR. YY1 conditional knockout caused differential expression of 1129 genes, with 59 being mitochondrial-related genes. ChIP-seq analyses showed YY1 was directly bound to nearly half of these mitochondrial-related genes. Surprisingly, at the time when YY1 knockout dramatically reduces DNA loop formation and CSR, mitochondrial mass and membrane potential were not significantly impacted, nor was there a significant change in mitochondrial oxygen consumption, extracellular acidification rate, or mitochondrial complex I or IV activities. Our results indicate that YY1 regulates numerous mitochondrial-related genes in splenic B cells, but this does not account for the impact of YY1 on CSR or long-distance DNA loop formation.


Assuntos
Linfócitos B/imunologia , DNA Mitocondrial/imunologia , Genes Mitocondriais/imunologia , Switching de Imunoglobulina , Baço/imunologia , Fator de Transcrição YY1/imunologia , Animais , Linfócitos B/citologia , DNA Mitocondrial/genética , Camundongos , Camundongos Knockout , Baço/citologia , Fator de Transcrição YY1/genética
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