Cathepsin L stabilizes the histone modification landscape on the Y chromosome and pericentromeric heterochromatin
Cathepsin L stabilizes the histone modification landscape on the Y chromosome and pericentromeric heterochromatin
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DOI：
10.1128/mcb.00135-06
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发表时间：
2006-06-01
影响因子：
5.3
通讯作者：
Grigoryev, Sergei A.
中科院分区：
文献类型：
--
作者：
Bulynko, Yaroslava A.;Hsing, Lianne C.;Grigoryev, Sergei A.
在哺乳动物染色体上，所有组蛋白修饰和组蛋白变体形成独特的表观遗传景观，其中主要的表观遗传异染色质标记物三甲基化组蛋白H3（K9）和组蛋白H2A.Z相对于彼此反向定位。三甲基化的H3（K9）标志着着丝粒周围的组成性异染色质和男性Y染色体，而H2A.Z在这些染色体位置显着减少。溶酶体和核蛋白酶，组织蛋白酶L的失活，导致表观遗传标记的全球重新分布。在组织蛋白酶L敲除细胞中，三甲基化H3（K9）的水平显著降低，伴随着其远离异染色质的重新定位，并且H2A.Z在着丝粒周围异染色质和Y染色体处变得富集。这种变化也与异染色质蛋白HP 1和组蛋白H3甲基转移酶Suv 39 h1远离组成型异染色质的全局重新定位有关;然而，它不影响DNA甲基化或染色体分离，这些表型通常与受损的组蛋白H3（K9）甲基化相关。因此，关键的组成性异染色质决定簇可以根据生理环境动态地重新分布，但仍然保持染色体的基本功能。因此，我们的数据表明，组织蛋白酶L通过一种新的机制，不涉及DNA甲基化或影响异染色质结构，并在体细胞和性染色体上操作，稳定了着丝粒周围异染色质和Y染色体上的表观遗传异染色质标记。
Posttranslationall histone modifications and histone variants form a unique epigenetic landscape on mammalian chromosomes where the principal epigenetic heterochromatin markers, trimethylated histone H3(K9) and the histone H2A.Z, are inversely localized in relation to each other. Trimethylated H3(K9) marks pericentromeric constitutive heterochromatin and the male Y chromosome, while H2A.Z is dramatically reduced at these chromosomal locations. Inactivation of a lysosomal and nuclear protease, cathepsin L, causes a global redistribution of epigenetic markers. In cathepsin L knockout cells, the levels of trimethylated H3(K9) decrease dramatically, concomitant with its relocation away from heterochromatin, and H2A.Z becomes enriched at pericentromeric heterochromatin and the Y chromosome. This change is also associated with global relocation of heterochromatin protein HP1 and histone H3 methyltransferase Suv39h1 away from constitutive heterochromatin; however, it does not affect DNA methylation or chromosome segregation, phenotypes commonly associated with impaired histone H3(K9) methylation. Therefore, the key constitutive heterochromatin determinants can dynamically redistribute depending on physiological context but still maintain the essential function(s) of chromosomes. Thus, our data show that cathepsin L stabilizes epigenetic heterochromatin markers on pericentromeric heterochromatin and the Y chromosome through a novel mechanism that does not involve DNA methylation or affect heterochromatin structure and operates on both somatic and sex chromosomes.