The Histone Variant MacroH2A is an Epigenetic Regulator of Key Developmental Genes

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2009 Sep 8

PMID 19734898

Citations 111

Authors

Marcus Buschbeck

Iris Uribesalgo

Indra Wibowo

Pau Rue

David Martin

Arantxa Gutierrez

Lluis Morey

Roderic Guigo

Hernan Lopez-Schier

Luciano Di Croce

Affiliations

Soon will be listed here.

Abstract

The histone variants macroH2A1 and macroH2A2 are associated with X chromosome inactivation in female mammals. However, the physiological function of macroH2A proteins on autosomes is poorly understood. Microarray-based analysis in human male pluripotent cells uncovered occupancy of both macroH2A variants at many genes encoding key regulators of development and cell fate decisions. On these genes, the presence of macroH2A1+2 is a repressive mark that overlaps locally and functionally with Polycomb repressive complex 2. We demonstrate that macroH2A1+2 contribute to the fine-tuning of temporal activation of HOXA cluster genes during neuronal differentiation. Furthermore, elimination of macroH2A2 function in zebrafish embryos produced severe but specific phenotypes. Taken together, our data demonstrate that macroH2A variants constitute an important epigenetic mark involved in the concerted regulation of gene expression programs during cellular differentiation and vertebrate development.

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