The epigenetic H3S10 phosphorylation mark is required for counteracting heterochromatic spreading and gene silencing in Drosophila melanogaster
The epigenetic H3S10 phosphorylation mark is required for counteracting heterochromatic spreading and gene silencing in Drosophila melanogaster
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DOI：
10.1242/jcs.092585
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发表时间：
2011-12-15
影响因子：
4
通讯作者：
Johansen, Kristen M.
中科院分区：
文献类型：
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作者：
Wang, Chao;Cai, Weili;Johansen, Kristen M.
JIL-1激酶特异性定位于多粒染色体的常染色质带间区域，是在间期负责组蛋白H3S10磷酸化的激酶。与JIL-1强亚型功能缺失等位基因的遗传互作分析表明，JIL-1蛋白可以抵消主要异染色质成分对位置效应杂色（PEV）和基因沉默的影响。然而，目前尚不清楚这是否是表观遗传H3S10磷酸化标记的致病作用，还是JIL-1蛋白对PEV的影响实际上是由蛋白质的其他功能或结构特征引起的。通过转基因表达各种截断的JIL-1，无论是否具有激酶活性，并评估它们对PEV和异色扩散的影响，我们表明，在JIL-1零突变体中观察到的多染色体形态的总体扰动与PEV中的基因沉默无关，可能是由于多染色体排列和/或组织错误造成的，与染色质结构的表观遗传调控分开。此外，研究结果提供了证据，表明表观遗传H3S10磷酸化标记本身对于防止所观察到的异色扩散是必要的，而不依赖于JIL-1蛋白的任何结构贡献。
The JIL-1 kinase localizes specifically to euchromatin interband regions of polytene chromosomes and is the kinase responsible for histone H3S10 phosphorylation at interphase. Genetic interaction assays with strong JIL-1 hypomorphic loss-of-function alleles have demonstrated that the JIL-1 protein can counterbalance the effect of the major heterochromatin components on position-effect variegation (PEV) and gene silencing. However, it is unclear whether this was a causative effect of the epigenetic H3S10 phosphorylation mark, or whether the effect of the JIL-1 protein on PEV was in fact caused by other functions or structural features of the protein. By transgenically expressing various truncated versions of JIL-1, with or without kinase activity, and assessing their effect on PEV and heterochromatic spreading, we show that the gross perturbation of polytene chromosome morphology observed in JIL-1 null mutants is unrelated to gene silencing in PEV and is likely to occur as a result of faulty polytene chromosome alignment and/or organization, separate from epigenetic regulation of chromatin structure. Furthermore, the findings provide evidence that the epigenetic H3S10 phosphorylation mark itself is necessary for preventing the observed heterochromatic spreading independently of any structural contributions from the JIL-1 protein.