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Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE212120 | GEO | 2022/09/30

REPOSITORIES: GEO

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Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I [leChRO-seq]

Project description:During meiotic prophase I, germ cells must balance transcriptional activation with meiotic recombination and chromosome synapsis, biological processes requiring extensive changes to chromatin state and structure. Here we explored the interplay between chromatin accessibility and transcription across a detailed time-course of murine male meiosis by measuring genome-wide patterns of chromatin accessibility, transcription, and processed mRNA. To understand the relationship between these parameters of gene regulation and recombination, we integrated these data with maps of double-strand break formation. Maps of nascent transcription showed that Pol II is loaded on chromatin and maintained in a paused state early during meiosis. In pachynema, paused Pol II is released in a coordinated transcriptional burst resulting in ~3-fold increase in transcription. Release from pause is mediated by the transcription factor A-MYB and the testis-specific bromodomain protein, BRDT. The burst of transcriptional activity is both temporally and spatially segregated from key steps of meiotic recombination: double strand breaks show evidence of chromatin accessibility earlier during prophase I and at distinct loci from those undergoing transcriptional activation, despite shared chromatin marks. Our findings uncover the mechanisms of transcriptional activation and how cells compartmentalize transcription and recombination during meiosis.

2022-09-30 | GSE212118 | GEO

Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I [RNA-Seq]

2022-09-30 | GSE212116 | GEO

Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I [ATAC-Seq]

2022-09-30 | GSE212117 | GEO

A-MYB and BRDT-dependent RNA Polymerase II pause release orchestrates transcriptional regulation in mammalian meiosis.

Project description:During meiotic prophase I, spermatocytes must balance transcriptional activation with homologous recombination and chromosome synapsis, biological processes requiring extensive changes to chromatin state. We explored the interplay between chromatin accessibility and transcription through prophase I of mammalian meiosis by measuring genome-wide patterns of chromatin accessibility, nascent transcription, and processed mRNA. We find that Pol II is loaded on chromatin and maintained in a paused state early during prophase I. In later stages, paused Pol II is released in a coordinated transcriptional burst mediated by the transcription factors A-MYB and BRDT, resulting in ~3-fold increase in transcription. Transcriptional activity is temporally and spatially segregated from key steps of meiotic recombination: double strand breaks show evidence of chromatin accessibility earlier during prophase I and at distinct loci from those undergoing transcriptional activation, despite shared chromatin marks. Our findings reveal mechanisms underlying chromatin specialization in either transcription or recombination in meiotic cells.

| S-EPMC10060231 | biostudies-literature

Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I

Project description:Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I

| PRJNA874041 | ENA

Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I [RNA-Seq]

Project description:Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I [RNA-Seq]

| PRJNA874045 | ENA

Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I [ATAC-Seq]

Project description:Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I [ATAC-Seq]

| PRJNA874047 | ENA

Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I [leChRO-seq]

Project description:Meiotic gene transcription programs are mediated by A-MYB and BRDT-dependent RNA Pol II pause release during mammalian prophase I [leChRO-seq]

| PRJNA874046 | ENA

Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF.

Project description:Enhancer RNAs (eRNAs) are long non-coding RNAs that originate from enhancers. Although eRNA transcription is a canonical feature of activated enhancers, the molecular features required for eRNA function and the mechanism of how eRNAs impinge on target gene transcription have not been established. Thus, using eRNA-dependent RNA polymerase II (Pol II) pause release as a model, we here investigate the requirement of sequence, structure and length of eRNAs for their ability to stimulate Pol II pause release by detaching NELF from paused Pol II. We find eRNAs not to exert their function through common structural or sequence motifs. Instead, eRNAs that exhibit a length >200 nucleotides and that contain unpaired guanosines make multiple, allosteric contacts with NELF subunits -A and -E to trigger efficient NELF release. By revealing the molecular determinants of eRNA function, our study establishes eRNAs as an important player in Pol II pause release, and it provides new insight into the regulation of metazoan transcription.

| S-EPMC9068813 | biostudies-literature

NELF Regulates a Promoter-Proximal Step Distinct from RNA Pol II Pause-Release.

Project description:RNA polymerase II (RNA Pol II) is generally paused at promoter-proximal regions in most metazoans, and based on in vitro studies, this function has been attributed to the negative elongation factor (NELF). Here, we show that upon rapid depletion of NELF, RNA Pol II fails to be released into gene bodies, stopping instead around the +1 nucleosomal dyad-associated region. The transition to the 2nd pause region is independent of positive transcription elongation factor P-TEFb. During the heat shock response, RNA Pol II is rapidly released from pausing at heat shock-induced genes, while most genes are paused and transcriptionally downregulated. Both of these aspects of the heat shock response remain intact upon NELF loss. We find that NELF depletion results in global loss of cap-binding complex from chromatin without global reduction of nascent transcript 5' cap stability. Thus, our studies implicate NELF functioning in early elongation complexes distinct from RNA Pol II pause-release.

| S-EPMC7402197 | biostudies-literature

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