Step-Wise Methylation of Histone H3K9 Positions Heterochromatin at the Nuclear Periphery
Step-Wise Methylation of Histone H3K9 Positions Heterochromatin at the Nuclear Periphery
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DOI：
10.1016/j.cell.2012.06.051
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发表时间：
2012-08-31
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：
Towbin, Benjamin D.;Gonzalez-Aguilera, Cristina;Gasser, Susan M.
目前还不清楚在核周围隔离转录抑制的异染色质的因素。在全基因组RNAi筛选中，我们发现S-腺苷甲硫氨酸（SAM）合成酶的缺失降低了组蛋白甲基化，并导致秀丽隐杆线虫胚胎中异染色质从核周边的去抑制和释放。组蛋白甲基转移酶（HMT）的分析表明，消除两个HMT，MET-2和SET-25，模拟SAM合成酶的损失，废除异染色质转基因和天然染色体臂的核周附着丰富的组蛋白H3赖氨酸9甲基化。这两种HMT以连续的方式靶向H3 K9：MET-2，一种SETDB 1同系物，介导单和二甲基化，而SET-25，一种以前未表征的HMT，沉积H3 K9 me 3。SET-25与其自身的产物共定位在核周灶中，以依赖于H3 K9 me 3的方式，但不依赖于其催化结构域。这种共定位表明一个自主的，自我加强的机制，建立和繁殖的重复丰富的异染色质。
The factors that sequester transcriptionally repressed heterochromatin at the nuclear periphery are currently unknown. In a genome-wide RNAi screen, we found that depletion of S-adenosylmethionine (SAM) synthetase reduces histone methylation globally and causes derepression and release of heterochromatin from the nuclear periphery in Caenorhabditis elegans embryos. Analysis of histone methyltransferases (HMTs) showed that elimination of two HMTs, MET-2 and SET-25, mimics the loss of SAM synthetase, abrogating the perinuclear attachment of heterochromatic transgenes and of native chromosomal arms rich in histone H3 lysine 9 methylation. The two HMTs target H3K9 in a consecutive fashion: MET-2, a SETDB1 homolog, mediates mono-and dimethylation, and SET-25, a previously uncharacterized HMT, deposits H3K9me3. SET-25 colocalizes with its own product in perinuclear foci, in a manner dependent on H3K9me3, but not on its catalytic domain. This colocalization suggests an autonomous, self-reinforcing mechanism for the establishment and propagation of repeat-rich heterochromatin.