Reduced levels of Su(var)3-9 but not Su(var)2-5 (HP1) counteract the effects on chromatin structure and viability in loss-of-function mutants of the JIL-1 histone H3S10 kinase
Reduced levels of Su(var)3-9 but not Su(var)2-5 (HP1) counteract the effects on chromatin structure and viability in loss-of-function mutants of the JIL-1 histone H3S10 kinase
复制标题
DOI：
10.1534/genetics.107.075143
复制
发表时间：
2007-09-01
期刊：
影响因子：
3.3
通讯作者：
Johansen, Kristen M.
中科院分区：
文献类型：
--
作者：
Deng, Huai;Bao, Xiaomin;Johansen, Kristen M.
最近已经证明，必需的JIL-1组蛋白H3 S10激酶的活性是染色质结构的主要调节剂，并且其功能是维持常染色质结构域，同时抵消异染色质化和基因沉默。在缺乏JIL-1激酶活性的情况下，主要的异染色质标记物组蛋白H3 K9 me 2和HP 1串联扩散到染色体臂上的异位位置。在这项研究中，我们表明，在很大程度上，可以通过减少Su（var）3-9基因的剂量来挽救与无效JIL-1表型相关的致死性以及一些染色体形态缺陷。在Su（var）3-9的三个不同等位基因中观察到这种效应，强烈表明它对Su（var）3-9特异，而不是对第二位点修饰剂特异。这与用果蝇中编码HP 1的Su（var）2-5基因的等位基因进行的类似实验相反，其中在JIL-1和Su（var）2-5之间没有检测到遗传相互作用。总之，这些发现表明，虽然Su（var）3-9组蛋白甲基转移酶活性是与JIL-1组蛋白H3 S10激酶丧失相关的致死性和染色质结构扰动的主要因素，但这些作用可能与HP 1解偶联。
It has recently been demonstrated that activity of the essential JIL-1 histone H3S10 kinase is a major regulator of chromatin structure and that it functions to maintain euchromatic domains while counteracting heterochromatization and gene silencing. In the absence of JIL-1 kinase activity, the major heterochromatin markers histone H3K9me2 and HP1 spread in tandem to ectopic locations on the chromosome arms. In this study, we show that the lethality as well as some of the chromosome morphology defects associated with the null JIL-1 phenotype to a large degree can be rescued by reducing the dose of the Su(var)3-9 gene. This effect was observed with three different alleles of Su(var)3-9, strongly suggesting it is specific to Su(var)3-9 and not to second site modifiers. This is in contrast to similar experiments performed with alleles of the Su(var)2-5 gene that codes for HP1 in Drosophila where no genetic interactions were detectable between JIL-1 and Su(var)2-5. Taken together, these findings indicate that while Su(var)3-9 histone methyltransferase activity is a major factor in the lethality and chromatin structure perturbations associated with loss of the JIL-1 histone H3S10 kinase, these effects are likely to be uncoupled from HP1.