The histone variant macroH2A is an epigenetic regulator of key developmental genes

Marcus Buschbeck, Iris Uribesalgo, Indra Wibowo, Pau Rué, David Martin, Arantxa Gutierrez, Lluís Morey, Roderic Guigó, Hernán López-Schier, Luciano Di Croce

Research output: Contribution to journalArticlepeer-review

145 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1074-1079
Number of pages6
JournalNature Structural and Molecular Biology
Issue number10
StatePublished - Oct 2009
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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