ASH2L Regulates Ubiquitylation Signaling to MLL: Trans-regulation of H3 K4 Methylation in Higher Eukaryotes

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2013 Mar 5

PMID 23453805

Citations 45

Authors

Lipeng Wu

Shirley Y Lee

Bo Zhou

Uyen T T Nguyen

Tom W Muir

Song Tan

Yali Dou

Affiliations

Soon will be listed here.

Abstract

Crosstalk between H2B ubiquitylation (H2Bub) and H3 K4 methylation plays important roles in coordinating functions of diverse cofactors during transcription activation. The underlying mechanism for this trans-tail signaling pathway is poorly defined in higher eukaryotes. Here, we show the following: (1) ASH2L in the MLL complex is essential for H2Bub-dependent H3 K4 methylation. Deleting or mutating K99 of the N-terminal winged helix (WH) motif in ASH2L abrogates H2Bub-dependent regulation. (2) Crosstalk can occur in trans and does not require ubiquitin to be on nucleosomes or histones to exert regulatory effects. (3) trans-regulation by ubiquitin promotes MLL activity for all three methylation states. (4) MLL3, an MLL homolog, does not respond to H2Bub, highlighting regulatory specificity for MLL family histone methyltransferases. Altogether, our results potentially expand the classic histone crosstalk to nonhistone proteins, which broadens the scope of chromatin regulation by ubiquitylation signaling.

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