R Loops Regulate Promoter-proximal Chromatin Architecture and Cellular Differentiation

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2015 Nov 10

PMID 26551076

Citations 101

Authors

Poshen B Chen

Hsiuyi V Chen

Diwash Acharya

Oliver J Rando

Thomas G Fazzio

Affiliations

Soon will be listed here.

Abstract

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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