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Publication : The PWWP2A Histone Deacetylase Complex Represses Intragenic Spurious Transcription Initiation in mESCs.

First Author  Wei G Year  2020
Journal  iScience Volume  23
Issue  11 Pages  101741
PubMed ID  33235983 Mgi Jnum  J:319943
Mgi Id  MGI:6867108 Doi  10.1016/j.isci.2020.101741
Citation  Wei G, et al. (2020) The PWWP2A Histone Deacetylase Complex Represses Intragenic Spurious Transcription Initiation in mESCs. iScience 23(11):101741
abstractText  Transcriptional fidelity depends on accurate promoter selection and initiation from the correct sites. In yeast, H3K36me3-mediated recruitment of the Rpd3S HDAC complex to gene bodies suppresses spurious transcription initiation. Here we describe an equivalent pathway in metazoans. PWWP2A/B is an H3K36me3 reader that forms a stable complex with HDAC1/2. We used CAGE-seq to profile all transcription initiation sites in wild-type mESCs and cells lacking PWWP2A/B. Loss of PWWP2A/B enhances spurious initiation from intragenic sites present in wild-type mESCs, and this effect is associated with increased levels of initiating Pol-II and histone acetylation. Spurious initiation events in Pwwp2a/b DKO mESCs do not overlap in genomic location or chromatin features with spurious sites that arise in Dnmt3b KO mESCs, previously reported to function in the suppression of intragenic transcriptional initiation, suggesting these pathways function cooperatively in maintaining the fidelity of transcription initiation in metazoans.
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