The histone variant macroH2A is an epigenetic regulator of key developmental genes.
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.
Buschbeck
Marcus
M
Centre de Regulació Genòmica (CRG), PRBB, Barcelona, Spain.
Uribesalgo
Iris
I
Wibowo
Indra
I
Rué
Pau
P
Martin
David
D
Gutierrez
Arantxa
A
Morey
Lluís
L
Guigó
Roderic
R
López-Schier
Hernán
H
Di Croce
Luciano
L
D000818:Animals; D019070:Cell Lineage; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006657:Histones / Q000737:chemistry* / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D015027:Zebrafish
D006657:Histones; D018398:Homeodomain Proteins; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; C120756:macroH2A histone; C088144:HoxA protein