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Mol Cell. 2017 Aug 17;67(4):594-607.e4. doi: 10.1016/j.molcel.2017.06.029. Epub 2017 Jul 20.

Mot1, Ino80C, and NC2 Function Coordinately to Regulate Pervasive Transcription in Yeast and Mammals.

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Department of Biological Chemistry, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Regenerative Medicine Center and Center for Molecular Medicine, University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
Department of Biological Chemistry, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA. Electronic address:


Pervasive transcription initiates from cryptic promoters and is observed in eukaryotes ranging from yeast to mammals. The Set2-Rpd3 regulatory system prevents cryptic promoter function within expressed genes. However, conserved systems that control pervasive transcription within intergenic regions have not been well established. Here we show that Mot1, Ino80 chromatin remodeling complex (Ino80C), and NC2 co-localize on chromatin and coordinately suppress pervasive transcription in S. cerevisiae and murine embryonic stem cells (mESCs). In yeast, all three proteins bind subtelomeric heterochromatin through a Sir3-stimulated mechanism and to euchromatin via a TBP-stimulated mechanism. In mESCs, the proteins bind to active and poised TBP-bound promoters along with promoters of polycomb-silenced genes apparently lacking TBP. Depletion of Mot1, Ino80C, or NC2 by anchor away in yeast or RNAi in mESCs leads to near-identical transcriptome phenotypes, with new subtelomeric transcription in yeast, and greatly increased pervasive transcription in both yeast and mESCs.


Ino80; Mot1; NC2; Sir3; heterochromatin; pervasive transcription; polycomb; promoter; silencing

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