Su(var) genes regulate the balance between euchromatin and heterochromatin in Drosophila
Su(var) genes regulate the balance between euchromatin and heterochromatin in Drosophila
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DOI：
10.1101/gad.323004
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发表时间：
2004-12-01
影响因子：
10.5
通讯作者：
Reuter, G
中科院分区：
文献类型：
--
作者：
Ebert, A;Schotta, G;Reuter, G
组蛋白赖氨酸甲基化是指示染色体亚结构域的表观遗传标记。在果蝇中，H3-K9的二甲基化和三甲基化主要由异染色质SU（VAR）3-9 HMTase控制，该酶是位置效应杂色（PEV）的主要调节剂。相反，H3-K27甲基化状态独立地由Pc-基团酶E（Z）介导。19个点突变体的分离表明Su（var）3-9的沉默潜力随着其相关的HMTase活性而增加。一种过度活跃的Su（var）3-9突变体，Pitkin（D），在臂间异染色质内以及臂间异染色质外显示出广泛的H3-K9二甲基化和三甲基化。值得注意的是，一个新的Su（var）基因Su（var）3-1的突变严重限制了Su（var）3-9介导的基因沉默。Su（var）3-1被鉴定为常染色质H3-S10激酶JIL-1的“反形”突变体。JIL-1（Su（var）3-1）突变体保持激酶活性并且不可检测地损害抑制性组蛋白赖氨酸甲基化标记。然而，用七种不同PEV重排的分析证明了JIL-1（Su（var）3-1）在控制异染色质致密化和扩增中的一般作用。我们的数据提供了证据，异染色质和常染色质之间的动态平衡，并定义两个不同的机制，苏（var）基因的功能。尽管大多数Su（var）编码异染色质的固有组分，可以建立抑制性染色质结构[内在Su（var）s]，但Su（var）3-1反映了常染色质组分的功能获得性突变体，其拮抗异染色质亚结构域的扩展[获得性Su（var）s]。
Histone lysine methylation is an epigenetic mark to index chromosomal subdomains. In Drosophila, H3-K9 di- and trimethylation is mainly controlled by the heterochromatic SU(VAR)3-9 HMTase, a major regulator of position-effect variegation (PEV). In contrast, H3-K27 methylation states are independently mediated by the Pc-group enzyme E(Z). Isolation of 19 point mutants demonstrates that the silencing potential of Su(var)3-9 increases with its associated HMTase activity. A hyperactive Su(var)3-9 mutant, pitkin(D), displays extensive H3-K9 di- and trimethylation within but also outside pericentric heterochromatin. Notably, mutations in a novel Su(var) gene, Su(var)3-1, severely restrict Su(var)3-9-mediated gene silencing. Su(var)3-1 was identified as "antimorphic" mutants of the euchromatic H3-S10 kinase JIL-1. JIL-1(Su(var)3-1) mutants maintain kinase activity and do not detectably impair repressive histone lysine methylation marks. However, analyses with seven different PEV rearrangements demonstrate a general role of JIL-1(Su(var)3-1) in controlling heterochromatin compaction and expansion. Our data provide evidence for a dynamic balance between heterochromatin and euchromatin, and define two distinct mechanisms for Su(var) gene function. Whereas the majority of Su(var)s encode inherent components of heterochromatin that can establish repressive chromatin structures [intrinsic Su(var)s], Su(var)3-1 reflects gain-of-function mutants of a euchromatic component that antagonize the expansion of heterochromatic subdomains [acquired Su(var)s].