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P53-dependent effects of DNA double-strand breaks on chromatin accessibility

ABSTRACT: We used ATAC-seq to detect changes in chromatin accessibility and nucleosome positioning around the MYC gene during the DNA double-strand break response in human cells and the dependence of these changes on p53. We found that, in the region ~50 kb downstream of MYC where p53 binds strongly, chromatin accessibility as measured by ATAC-seq fragment density increased during the DNA DSB response, corresponding to the removal of a single nucleosome. These results are consistent with increased accessibility of a distal regulatory element at this locus that is dependent on DNA damage and p53 expression. At the MYC promoter region there is a p53-dependent decrease in chromatin accessibility in response to DSBs, even in the absence of a direct p53 binding site near the region. While both the P1 and P2 promoters of MYC are relatively free of nucleosomes in MCF-7 sh-p53 cells, both promoters are occluded in cells expressing WT levels of p53, with an increase of nucleosomal occlusion in response to DNA damage. This supports the hypothesis that MYC repression during the DNA DSB response results from nucleosomal occlusion of both the P1 and P2 promoters.

ORGANISM(S): Homo sapiens

PROVIDER: GSE101736 | GEO | 2017/08/02

SECONDARY ACCESSION(S): PRJNA395318

REPOSITORIES: GEO

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Ma2005-digital response of p53 to DNA damage-ATM Activation Module

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2020-05-13 | MODEL2005130001 | BioModels

Measuring the effect of MYC on transcription during the DNA double-strand break response by RNA-seq of newly synthesized transcripts

Project description:We sequenced newly synthesized mRNA to determine which genes are differentially transcribed during the DNA double-strand break (DSB) response. Moreover, as the transcription factor MYC is repressed in a p53-dependent manner during the DSB response, we determined the effect of this repression on transcription by maintaining MYC above its basal expression level. To control for differences in cell size, we spiked in S. pombe RNA proportional to cell number, then normalized human transcript counts to S. pombe transcript counts. We found that ~77% of transcripts were produced at a lower level during the time interval 2.5‑3.5 h after treatment with neocarzinostatin (NCS), which causes DSBs, than in a one-hour time interval without NCS treatment. When MYC was maintained above its basal level during the DSB response, only ~59% of transcripts were produced at a lower level in NCS-treated cells. Known p53 target genes were upregulated during the same time interval, and maintaining MYC above its basal level did not change this significantly. Consistent with previous observations, we found that increasing MYC levels increased transcription of most genes, with a larger effect on more highly transcribed genes. We observed the opposite in NCS-treated cells, in which more highly transcribed genes were downregulated to a greater degree. These data support a model that p53, by repressing MYC, redistributes transcription during the DSB response, inhibiting global transcription while activating transcription of specific genes involved in the response.

2017-08-02 | GSE101738 | GEO

ATM suppresses c-Myc overexpression in the mammary epithelium in response to estrogen

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2023-06-01 | GSE218320 | GEO

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2023-05-10 | GSE231538 | GEO

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2019-11-11 | PXD014618 | Pride

Developmentally regulated isoform of HNF4α reprograms the adult liver

Project description:Hepatocyte Nuclear Factor 4α (HNF4α), master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2). P1-HNF4α but not P2-HNF4α is expressed in normal adult liver while both P1- and P2-HNF4α are expressed in fetal liver and liver cancer. To determine the physiological function of the HNF4α isoforms, we compared P2-HNF4α-expressing exon swap mice to wildtype (WT) using RNA-seq, ChIP-seq, proteomics, protein binding microarrays (PBMs) and metabolomics. P2-HNF4α orchestrates a distinct transcriptomic and metabolomic profile.

2018-08-31 | GSE117972 | GEO

ib101206 - proteome data analysis

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2018-03-19 | PXD003287 | Pride

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2022-09-13 | PXD034446 | Pride

RNAseq for subpopulations of adipose tissue stromal cells from mouse inguinal adipose tissue

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