Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination.

Abstract:

:Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adaptor protein WDR82 and its associated complexes actively limit such non-coding transcription. WDR82 targets the SET1 H3K4 methyltransferases and the nuclear protein phosphatase 1 (PP1) complexes to the initiating Pol II. WDR82 and PP1 also interact with components of the transcriptional termination and RNA processing machineries. Depletion of WDR82, SET1, or the PP1 subunit required for its nuclear import caused distinct but overlapping transcription termination defects at highly expressed genes and active enhancers and promoters, thus enabling the increased synthesis of unusually long ncRNAs. These data indicate that transcription initiated from cis-regulatory elements is tightly coordinated with termination mechanisms that impose the synthesis of short RNAs.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Austenaa LM,Barozzi I,Simonatto M,Masella S,Della Chiara G,Ghisletti S,Curina A,de Wit E,Bouwman BA,de Pretis S,Piccolo V,Termanini A,Prosperini E,Pelizzola M,de Laat W,Natoli G

doi

10.1016/j.molcel.2015.09.018

subject

Has Abstract

pub_date

2015-11-05 00:00:00

pages

460-74

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(15)00738-8

journal_volume

60

pub_type

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