Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 22, Issue 12, Pages 999-1007Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3122
Keywords
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Funding
- US National Institutes of Health (NIH) [R01HD072122]
- American Cancer Society [RSG-14-220-01]
- NIH [R01HD080224, 1S10RR027052-01]
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Numerous chromatin-remodeling factors are regulated by interactions with RNA, although the contexts and functions of RNA binding are poorly understood. Here we show that R loops, RNA-DNA hybrids consisting of nascent transcripts hybridized to template DNA, modulate the binding of two key chromatin-regulatory complexes, Tip60-p400 and polycomb repressive complex 2 (PRC2) in mouse embryonic stem cells (ESCs). Like PRC2, the Tip60-p400 histone acetyltransferase complex binds to nascent transcripts; however, transcription promotes chromatin binding of Tip60-p400 but not PRC2. Interestingly, we observed higher Tip60-p400 and lower PRC2 levels at genes marked by promoter-proximal R loops. Furthermore, disruption of R loops broadly decreased Tip60-p400 occupancy and increased PRC2 occupancy genome wide. In agreement with these alterations, ESCs partially depleted of R loops exhibited impaired differentiation. These results show that R loops act both positively and negatively in modulating the recruitment of key pluripotency regulators.
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