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

Liv M I Austenaa, Iros Barozzi, Marta Simonatto, Silvia Masella, Giulia Della Chiara, Serena Ghisletti, Alessia Curina, Elzo de Wit, Britta A M Bouwman, Stefano de Pretis, Viviana Piccolo, Alberto Termanini, Elena Prosperini, Mattia Pelizzola, Wouter de Laat, Gioacchino Natoli

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)460-74
Number of pages15
JournalMolecular Cell
Volume60
Issue number3
DOIs
Publication statusPublished - 05 Nov 2015

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