Distinct dynamics and distribution of histone methyl-lysine derivatives in mouse development
Distinct dynamics and distribution of histone methyl-lysine derivatives in mouse development
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DOI：
10.1016/j.ydbio.2004.08.038
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发表时间：
2004-12-15
影响因子：
2.7
通讯作者：
Underhill, DA
中科院分区：
文献类型：
--
作者：
Biron, VL;McManus, KJ;Underhill, DA
组蛋白甲基化通过修饰组蛋白H3和H4上的精氨酸和赖氨酸残基作为染色质活性的表观遗传调节剂。在赖氨酸的情况下，这包括单-、二-或三甲基基团的形成，其中每一个被认为代表细胞水平上的不同功能状态。为了研究这些修饰的潜在发育作用，我们确定了妊娠中期小鼠胚胎中组蛋白H3上K9和组蛋白H4上K20的赖氨酸甲基化的全球模式。对于每个赖氨酸靶位点，我们观察到不同的亚核分布的单-和三甲基的版本在10 T 1/2细胞内保存的原代培养物和胚胎的三维组织结构。有趣的是，这些修饰中的三种，组蛋白H3三甲基K9，组蛋白H4单甲基K20和组蛋白H4三甲基K20在神经上皮内的分布中表现出显著差异。具体而言，历史H3三甲基K9和H4单甲基K20在神经管的增殖细胞中升高，在K9修饰的情况下，其仅限于管腔表面上的有丝分裂细胞。与此相反，历史H4三甲基K20从这些内侧区域逐渐丢失，并成为丰富的腹外侧神经管中的分化神经元。历史H4 K20甲基衍生物的反向关系在骨骼肌和心肌发生期间甚至更引人注目，其中在着丝粒周围异染色质中三甲基修饰的积累表明在有丝分裂后肌肉细胞中基因沉默中的作用。重要的是，我们的研究结果确定组蛋白赖氨酸甲基化以高度动态的方式发生，这与它们在细胞分裂和分化的表观遗传程序中的功能一致。(C)2004爱思唯尔公司All rights reserved.
Histone methylation acts as an epigenetic regulator of chromatin activity through the modification of arginine and lysine residues on histones H3 and H4. In the case of lysine, this includes the formation of mono-, di-, or trimethyl groups, each of which is presumed to represent a distinct functional state at the cellular level. To examine the potential developmental roles of these modifications, we determined the global patterns of lysine methylation involving K9 on histone H3 and K20 on histone H4 in midgestation mouse embryos. For each lysine target site, we observed distinct subnuclear distributions of the mono- and trimethyl versions in 10T 1/2 cells that were conserved within primary cultures and within the 3D-tissue architecture of the embryo. Interestingly, three of these modifications, histone H3 trimethyl K9, histone H4 monomethyl K20, and histone H4 trimethyl K20 exhibited marked differences in their distribution within the neuroepithelium. Specifically, both historic H3 trimethyl K9 and H4 monomethyl K20 were elevated in proliferating cells of the neural tube, which in the case of the K9 modification was limited to mitotic cells on the luminal surface. In contrast, historic H4 trimethyl K20 was progressively lost from these medial regions and became enriched in differentiating neurons in the ventrolateral neural tube. The inverse relationship of historic H4 K20 methyl derivatives is even more striking during skeletal and cardiac myogenesis where the accumulation of the trimethyl modification in pericentromeric heterochromatin suggests a role in gene silencing in postmitotic muscle cells. Importantly, our results establish that histone lysine methylation occurs in a highly dynamic manner that is consistent with their function in an epigenetic program for cell division and differentiation. (C) 2004 Elsevier Inc. All rights reserved.