Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans Embryos
Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans Embryos
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DOI：
10.1016/j.cell.2015.10.066
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发表时间：
2015-12-06
期刊：
影响因子：
64.5
通讯作者：
Gasser, Susan M.
中科院分区：
文献类型：
--
作者：
Gonzalez-Sandoval, Adriana;Towbin, Benjamin D.;Gasser, Susan M.
间期染色质被组织成不同的核亚室，反映其紧凑程度和转录状态。在秀丽线虫胚胎中，H3K9甲基化是沉默和在核外围锚定富含重复序列的异染色质所必需的。在异染色质核周锚定的筛选中，我们发现了一种以前未鉴定的线虫染色域蛋白CEC-4。CEC-4优先结合单甲基化、双甲基化或三甲基化的H3K9，并独立于H3K9甲基化和核层粘连蛋白定位于核膜。CEC-4是内源性异染色质锚定所必需的，但不是转录抑制所必需的，这与蠕虫中其他已知的H3K9甲基结合蛋白不同，后者介导基因抑制，而不是核周锚定。当我们在胚胎中异位诱导肌肉分化程序时，CEC-4突变体无法完全决定肌肉细胞的命运。这表明，在发育过程中染色质的核周隔离通过稳定对特定细胞命运的承诺来帮助限制细胞分化计划。
Interphase chromatin is organized in distinct nuclear sub-compartments, reflecting its degree of compaction and transcriptional status. In Caenorhabditis elegans embryos, H3K9 methylation is necessary to silence and to anchor repeat-rich heterochromatin at the nuclear periphery. In a screen for perinuclear anchors of heterochromatin, we identified a previously uncharacterized C. elegans chromodomain protein, CEC-4. CEC-4 binds preferentially mono-, di-, or tri-methylated H3K9 and localizes at the nuclear envelope independently of H3K9 methylation and nuclear lamin. CEC-4 is necessary for endogenous heterochromatin anchoring, but not for transcriptional repression, in contrast to other known H3K9 methyl-binders in worms, which mediate gene repression but not perinuclear anchoring. When we ectopically induce a muscle differentiation program in embryos, cec-4 mutants fail to commit fully to muscle cell fate. This suggests that perinuclear sequestration of chromatin during development helps restrict cell differentiation programs by stabilizing commitment to a specific cell fate.