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Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1 [SLAM-seq]

ABSTRACT: Using SLAM-seq to capture de novo synthesized polyadenylated RNAs, we quantitated changes in nascent RNA expression, as well as in total RNA expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE171133 | GEO | 2021/11/11

REPOSITORIES: GEO

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Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1 [SLAM-seq]

Project description:Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1 [SLAM-seq]

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Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1

Project description:This SuperSeries is composed of the SubSeries listed below.

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Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1 [ChIP-seq]

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Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1

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Project description:Defining direct targets of transcription factors and regulatory pathways is key to understanding their role in physiology and disease. Here we combine SLAM-seq, a novel method for direct quantification of newly synthesized mRNAs, with pharmacological and rapid chemical-genetic perturbation to interrogate primary transcriptional targets of BRD4 and MYC and define the response to BET bromodomain inhibitors (BETi). While BRD4 acts as a global co-activator of Pol2-dependent transcription in a BET bromodomain-dependent manner, therapeutic BETi doses deregulate a small set of hypersensitive target genes. In contrast to BRD4, MYC primarily acts as a selective transcriptional activator that controls basic metabolic processes such as ribosome biogenesis and de-novo purine synthesis across diverse cancer contexts. Beyond defining primary regulatory functions of BRD4 and MYC in cancer, our study establishes a simple, robust and scalable approach to dissect direct transcriptional targets of any gene or pathway.

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