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H3K4 methylation at active genes mitigates transcription-replication conflicts during replication stress

ABSTRACT: H3K4 methylation at active genes mitigates transcription-replication conflicts during replication stress

PROVIDER: PRJNA550410 | ENA |

REPOSITORIES: ENA

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H3K4 methylation at active genes mitigates transcription-replication conflicts during replication stress

Project description:Methylated H3K4 (H3K4me) is highly conserved and has been widely considered to be involved in transcriptional control. However, this once popular model was recently challenged by multiple groups, because blocking this modification does not appreciably affect transcription. Thus, the function of the H3K4me remains unclear. To investigate how H3K4 methylation influences the processes of transcription and replication under HU-stress, we used chromatin immunoprecipitation-sequencing (ChIP-seq) to identify genomic sites of active transcription marked by Rpb3, a subunit of RNA Polymerase II, and sites of replication pausing marked by DNA Pol2, a subunit of DNA Polymerase e. Our data lead us to the surprising conclusion that H3K4me pauses the progression of replication forks, and we propose that high levels of H3K4me deposited by high transcriptional activity result in a large cushioning effect on fork progression to protect against transcription-replication collisions (TRCs), which cause genome instability.

2019-08-31 | GSE133222 | GEO

H3K4 methylation at active genes mitigates transcription-replication conflicts during replication stress.

Project description:Transcription-replication conflicts (TRCs) occur when intensive transcriptional activity compromises replication fork stability, potentially leading to gene mutations. Transcription-deposited H3K4 methylation (H3K4me) is associated with regions that are susceptible to TRCs; however, the interplay between H3K4me and TRCs is unknown. Here we show that H3K4me aggravates TRC-induced replication failure in checkpoint-defective cells, and the presence of methylated H3K4 slows down ongoing replication. Both S-phase checkpoint activity and H3K4me are crucial for faithful DNA synthesis under replication stress, especially in highly transcribed regions where the presence of H3K4me is highest and TRCs most often occur. H3K4me mitigates TRCs by decelerating ongoing replication, analogous to how speed bumps slow down cars. These findings establish the concept that H3K4me defines the transcriptional status of a genomic region and defends the genome from TRC-mediated replication stress and instability.

| S-EPMC7010754 | biostudies-literature

The MYCN oncoprotein resolves conflicts of stalling RNA Polymerase with the replication fork [DP_EXOSC10_Screen]

Project description:During the S-phase, conflicts of replication forks with RNA Polymerase II (RNAPII) threaten genomic stability. While the PAF complex can resolve such conflicts during elongation, the particularly deleterious conflicts with stalling RNAPII are resolved by an as of yet unknown mechanism. Here we show that the MYCN oncoprotein forms a ternary complex with RNAPII and the nuclear RNA exosome, a 3’‑5’ exoribonuclease complex. Together with TFIIS, this complex restarts promoter‑proximal RNAPII, allows escape from co-directional transcription-replication conflicts and prevents double‑strand break accumulation. In cells lacking RNA exosome function, MYCN globally terminates transcription. MYCN-mediated termination is triggered by ATM‑dependent recruitment of BRCA1, which then stabilizes nuclear mRNA decapping complexes. Disruption of mRNA decapping activates ATR, indicative of head-on transcription-replication conflicts, and inhibits DNA replication. We propose that MYCN resolves transcription-replication conflicts via this two-step mechanism to sustain the rapid proliferation of neuroendocrine tumor cells.

2021-12-10 | GSE164568 | GEO

The MYCN oncoprotein resolves conflicts of stalling RNA Polymerase with the replication fork [DP_EXOSC10_ChIP_4sUseq]

2021-12-10 | GSE164555 | GEO

The MYCN oncoprotein resolves conflicts of stalling RNA Polymerase with the replication fork [DP_EXOSC10_BLISS]

2021-12-10 | GSE164567 | GEO

CDK12 prevents MYC-induced transcription-replication conflicts

Project description:CDK12 prevents MYC-induced transcription-replication conflicts

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The yeast and human FACT complexes resolve R-loop-mediated transcription-replication conflicts

Project description:Transcription is a major obstacle for replication fork progression and transcription-replication collisions constitute a main cause of genome instability. At a genome-wide scale these obstacles can be detected by the accumulation of the replicative Rrm3 helicase required for RF progression through protein obstacles. Here we show that FACT, a chromatin-reorganizing complex that swaps nucleosomes around the RNA polymerase during transcription elongation and that also has a role in replication, is needed to resolve transcription-replication conflicts in Saccharomyces cerevisiae. Importantly, ChIP-chip analyses of Rrm3 reveal that replication progression impairment in FACT mutants occur genome-wide, but preferentially at highly transcribed regions. ChIP-chip studies were perfomed with antibodies against Rrm3-FLAG in the yeast S. cerevisiae.

2014-03-17 | E-GEOD-51653 | biostudies-arrayexpress

CDK12 prevents MYC-induced transcription-replication conflicts [BLISS]

Project description:CDK12 prevents MYC-induced transcription-replication conflicts [BLISS]

| PRJNA991555 | ENA

CDK12 prevents MYC-induced transcription-replication conflicts [EdU-seq]

Project description:CDK12 prevents MYC-induced transcription-replication conflicts [EdU-seq]

| PRJNA991567 | ENA

CDK12 prevents MYC-induced transcription-replication conflicts [RNA-seq]

Project description:CDK12 prevents MYC-induced transcription-replication conflicts [RNA-seq]

| PRJNA991550 | ENA