The Cul4-Ddb1(Cdt)² ubiquitin ligase inhibits invasion of a boundary-associated antisilencing factor into heterochromatin.
The Cul4-Ddb1(Cdt)² ubiquitin ligase inhibits invasion of a boundary-associated antisilencing factor into heterochromatin.
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DOI：
10.1016/j.cell.2010.11.051
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发表时间：
2011-01-07
期刊：
影响因子：
64.5
通讯作者：
Madhani HD
中科院分区：
文献类型：
--
作者：
Braun S;Garcia JF;Rowley M;Rougemaille M;Shankar S;Madhani HD
将染色体划分为常染色质和异染色质域需要指定边界的机制。色葡萄粟酒裂殖酵母JmjC家族蛋白Epe 1防止异染色质的异位扩散，并且其本身集中在边界处。特异性地，Epe 1被分布在异染色质中的HP 1沉默因子募集到异染色质中。我们在这里证明，选择性富集的Epe 1在边界需要其调节的保守Cul 4-Ddb 1Cdt 2泛素连接酶，直接识别Epe 1，并促进其多泛素化和降解。引人注目的是，在缺乏连接酶的细胞中，Epe 1持续存在于异染色质体内，从而诱导基因沉默的缺陷。Epe 1是Cul 4-Ddb 1Cdt 2复合物的唯一靶标，其破坏对于异染色质的保存是必要的。该机制与CK 2磷酸化HP 1/Swi 6以限制Epe 1平行起作用。我们的结论是，泛素依赖的雕塑的染色体分布的抗沉默因子是异染色质边界正确形成的关键。
Partitioning of chromosomes into euchromatic and heterochromatic domains requires mechanisms that specify boundaries. The S. pombe JmjC family protein Epe1 prevents the ectopic spread of heterochromatin and is itself concentrated at boundaries. Paradoxically, Epe1 is recruited to heterochromatin by HP1 silencing factors that are distributed throughout heterochromatin. We demonstrate here that the selective enrichment of Epe1 at boundaries requires its regulation by the conserved Cul4-Ddb1Cdt2 ubiquitin ligase, which directly recognizes Epe1 and promotes its polyubiquitylation and degradation. Strikingly, in cells lacking the ligase, Epe1 persists in the body of heterochromatin thereby inducing a defect in gene silencing. Epe1 is the sole target of the Cul4-Ddb1Cdt2 complex whose destruction is necessary for the preservation of heterochromatin. This mechanism acts parallel with phosphorylation of HP1/Swi6 by CK2 to restrict Epe1. We conclude that the ubiquitin-dependent sculpting of the chromosomal distribution of an antisilencing factor is critical for heterochromatin boundaries to form correctly.
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