Multiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome
Multiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome
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DOI：
10.1073/pnas.0408021101
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发表时间：
2004-12-14
影响因子：
11.1
通讯作者：
Willard, HF
中科院分区：
文献类型：
--
作者：
Chadwick, BP;Willard, HF
异染色质是通过整个细胞周期中的凝结，后期的复制和基因不活跃的复制来经典定义的。兼性异染色质特别值得注意，因为它的形成受到细胞分化的发展。兼性异染色质的最广泛例子是哺乳动物无活性X染色体（XI）。各种组蛋白变体和共价组蛋白修饰已与定义XI异质态的组织有关，并且XI异染色质的特征被广泛解释为反映了基因沉默的冗余系统。 However, here we demonstrate that the human Xi is packaged into at least two nonoverlapping heterochromatin types, each characterized by specific Xi features: one defined by the presence of Xi-specific transcript RNA, the histone variant macroH2A, and histone H3 trimethylated at lysine 27 and the other defined by H3 trimethylated at lysine 9, heterochromatin protein 1, and histone H4在赖氨酸20处进行三甲基化。此外，在不同异染色质类型中包装的XI区域的特征是在后期后期的复制模式不同。在空间和时间上截然不同的领域中兼性异染色质的布置对XI的建立和维护具有影响，并添加了先前未经引起的表观遗传复杂性程度。
Heterochromatin is defined classically by condensation throughout the cell cycle, replication in late S phase and gene inactivity. Facultative heterochromatin is of particular interest, because its formation is developmentally regulated as a result of cellular differentiation. The most extensive example of facultative heterochromatin is the mammalian inactive X chromosome (Xi). A variety of histone variants and covalent histone modifications have been implicated in defining the organization of the Xi heterochromatic state, and the features of Xi heterochromatin have been widely interpreted as reflecting a redundant system of gene silencing. However, here we demonstrate that the human Xi is packaged into at least two nonoverlapping heterochromatin types, each characterized by specific Xi features: one defined by the presence of Xi-specific transcript RNA, the histone variant macroH2A, and histone H3 trimethylated at lysine 27 and the other defined by H3 trimethylated at lysine 9, heterochromatin protein 1, and histone H4 trimethylated at lysine 20. Furthermore, regions of the Xi packaged in different heterochromatin types are characterized by different patterns of replication in late S phase. The arrangement of facultative heterochromatin into spatially and temporally distinct domains has implications for both the establishment and maintenance of the Xi and adds a previously unsuspected degree of epigenetic complexity.