Linker histone H1 is essential for Drosophila development, the establishment of pericentric heterochromatin, and a normal polytene chromosome structure
Linker histone H1 is essential for Drosophila development, the establishment of pericentric heterochromatin, and a normal polytene chromosome structure
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DOI：
10.1101/gad.1749309
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发表时间：
2009-02-15
影响因子：
10.5
通讯作者：
Skoultchi, Arthur I.
中科院分区：
文献类型：
--
作者：
Lu, Xingwu;Wontakal, Sandeep N.;Skoultchi, Arthur I.
我们产生了果蝇的突变等位基因，其中连接体组蛋白H1的表达可以通过RNAi在很大范围内下调。当H1蛋白水平降低至野生型幼虫水平的20%时，在发育的晚期幼虫-蛹阶段发生致死。在这里，我们表明，H1在异染色质内或附近的基因调控中具有重要的功能。它是位置效应杂色（PEV）的强显性抑制基因。与PEV的其他抑制因子类似，H1同时参与常染色质基因的抑制和异染色质基因的激活，所述常染色质基因被带到臂间异染色质附近，所述异染色质基因依赖于它们的臂间定位以获得最大的转录活性。对H1缺失的唾液腺多线染色体的研究表明，H1参与了染色体结构和功能的几个基本方面。首先，H1是异染色质结构完整性和主要的臂间异染色质相关组蛋白标记（包括H3 K9 Me（2）和H4 K20 Me（2））的沉积或维持所必需的。第二，H1也发挥了意想不到的作用内复制的姐妹染色单体的对齐。最后，H1是必不可少的所有多线染色体的臂间区组织成一个单一的染色中心。因此，接头组蛋白H1在果蝇中是必不可少的，并在体内染色体的结构和活性中起着重要作用。
We generated mutant alleles of Drosophila melanogaster in which expression of the linker histone H1 can be down-regulated over a wide range by RNAi. When the H1 protein level is reduced to; similar to 20% of the level in wildtype larvae, lethality occurs in the late larval - pupal stages of development. Here we show that H1 has an important function in gene regulation within or near heterochromatin. It is a strong dominant suppressor of position effect variegation (PEV). Similar to other suppressors of PEV, H1 is simultaneously involved in both the repression of euchromatic genes brought to the vicinity of pericentric heterochromatin and the activation of heterochromatic genes that depend on their pericentric localization for maximal transcriptional activity. Studies of H1-depleted salivary gland polytene chromosomes show that H1 participates in several fundamental aspects of chromosome structure and function. First, H1 is required for heterochromatin structural integrity and the deposition or maintenance of major pericentric heterochromatin-associated histone marks, including H3K9Me(2) and H4K20Me(2). Second, H1 also plays an unexpected role in the alignment of endoreplicated sister chromatids. Finally, H1 is essential for organization of pericentric regions of all polytene chromosomes into a single chromocenter. Thus, linker histone H1 is essential in Drosophila and plays a fundamental role in the architecture and activity of chromosomes in vivo.