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

doi:10.1038/nsmb.1665

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

137 Citations (Scopus)

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.

Original language	English
Journal	Nature Structural and Molecular Biology
ISSN	1545-9993
DOIs	https://doi.org/10.1038/nsmb.1665
Publication status	Published - 2009

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title = "The histone variant macroH2A is an epigenetic regulator of key developmental genes",

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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doi = "10.1038/nsmb.1665",

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T1 - The histone variant macroH2A is an epigenetic regulator of key developmental genes

AU - Buschbeck, Marcus

AU - Uribesalgo, Iris

AU - Wibowo, Indra

AU - Rué, Pau

AU - Martin, David

AU - Gutierrez, Arantxa

AU - Morey, Lluís

AU - Guigó, Roderic

AU - López-Schier, Hernán

AU - Di Croce, Luciano

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1038/nsmb.1665

DO - 10.1038/nsmb.1665

M3 - Journal article

C2 - 19734898

SN - 1545-9993

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

ER -

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

Abstract

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