Epigenetic Mechanisms of Groucho/Grg/TLE Mediated Transcriptional Repression

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2011 Dec 16

PMID 22169276

Citations 41

Authors

Sanjeevkumar R Patel

Samina S Bhumbra

Raghavendra S Paknikar

Gregory R Dressler

Affiliations

Soon will be listed here.

Abstract

The repression of transcription, through the concerted actions of tissue specific DNA binding proteins, Polycomb repressor complexes, and DNA methylation, is essential for maintaining stem cell pluripotency and for cell fate specification in development. In this report, we show that recruitment of the co-repressor protein Grg4 to a Pax DNA-binding site displaces the adaptor protein PTIP and a histone H3K4me complex. Grg4 recruits the arginine methyltransferase PRMT5 to chromatin resulting in symmetric H4R3 dimethylation. PRMT5 is essential for recruiting Polycomb proteins, in a Pax2/Grg4 dependent manner, which results in H3K27 methylation. These data define the early epigenetic events in response to Pax/Grg mediated gene repression and demonstrate that a single DNA binding protein can recruit either an activator or a repressor complex depending on the availability of Grg4. These data suggest a model for understanding the initiation of Groucho/Grg/TLE mediated gene silencing.

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