The histone variant macroH2A is an epigenetic regulator of key developmental genes
The histone variant macroH2A is an epigenetic regulator of key developmental genes
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DOI：
10.1038/nsmb.1665
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发表时间：
2009-10-01
影响因子：
16.8
通讯作者：
Di Croce, Luciano
中科院分区：
文献类型：
--
作者：
Buschbeck, Marcus;Uribesalgo, Iris;Di Croce, Luciano
组蛋白变体macroH2A1和macroH2A2与雌性哺乳动物的X染色体失活相关。然而，macroH2A蛋白在常染色体上的生理功能知之甚少。在人类男性多能细胞中进行的基于微阵列的分析揭示了两种macroH2A变体在编码发育和细胞命运决定的关键调节因子的许多基因中的占有率。在这些基因上，macroH2A1+2的存在是一种抑制性标记，与Polycomb抑制性复合物2在局部和功能上重叠。我们证明，macroH2A1+2有助于微调的时间激活HOXA簇基因在神经元分化。此外，消除斑马鱼胚胎中的macroH2A2功能产生了严重但特定的表型。两者合计，我们的数据表明，macroH2A变体构成了一个重要的表观遗传标记，参与细胞分化和脊椎动物发育过程中基因表达程序的协调调节。
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.