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The histone variant macroH2A is an epigenetic regulator of key developmental genes
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The histone variant macroH2A is an epigenetic regulator of key developmental genes
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Journal Article
The histone variant macroH2A is an epigenetic regulator of key developmental genes
2009
Overview
Nucleosomes can be modified by replacing the core histones with variants, the most diverse of which is macroH2A. The localization of macroH2A variants in human male pluripotent cells indicates that this variant functions in repression of key developmental genes and is essential for zebrafish embryogenesis.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
