Differential localization and independent acquisition of the H3K9me2 and H3K9me3 chromatin modifications in the Caenorhabditis elegans adult germ line.
Differential localization and independent acquisition of the H3K9me2 and H3K9me3 chromatin modifications in the Caenorhabditis elegans adult germ line.
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DOI：
10.1371/journal.pgen.1000830
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发表时间：
2010-01-22
期刊：
影响因子：
4.5
通讯作者：
Villeneuve AM
中科院分区：
文献类型：
--
作者：
Bessler JB;Andersen EC;Villeneuve AM
组蛋白甲基化是真核细胞染色质的一个重要特征，它调节着染色体功能的多个方面。甲基修饰可以发生在几个不同的氨基酸残基上，并且以不同的单甲基、二甲基和三甲基状态发生。然而，这些不同的修饰状态之间的相互作用还没有得到很好的理解。在这里，我们调查二甲基和三甲基修饰组蛋白H3（H3 K9 me 2和H3 K9 me 3）的赖氨酸9在成年秀丽隐杆线虫生殖系之间的关系。同时免疫荧光显示H3 K9 me 2和H3 K9 me 3的时间/空间定位模式非常不同。虽然H3 K9 me 2是丰富的未配对的性染色体，并通过减数分裂前期的生殖细胞的进展经历动态变化，我们在这里证明，H3 K9 me 3是不丰富的未配对的性染色体和本地化的所有染色体在所有生殖细胞在成年雌雄同体，直到初级精母细胞阶段的男性。此外，携带体细胞特异性启动子的高拷贝转基因阵列高度富集H3 K9 me 3（但不富集H3 K9 me 2），并且与DAPI微弱染色质结构域相关。我们进一步证明了H3 K9 me 2和H3 K9 me 3标记是独立获得的。MET-2是SETDB组蛋白甲基转移酶（HMTase）家族的成员，是所有可检测的生殖系H3 K9 me 2所必需的，但在成人生殖细胞中对H3 K9 me 3是无效的。相反，我们发现HMTase MES-2是一种负责成人生殖细胞中H3 K27甲基化的E（z）同源物，它是大多数生殖系H3 K9 me 3所必需的，但对H3 K9 me 2是不必要的。对MET-2突变体的表型分析表明，MET-2对生育力不是必需的，但抑制异位生殖细胞增殖，并有助于染色体遗传的保真度。我们对H3 K9 me 2和H3 K9 me 3的差异定位和独立获取的证明意味着H3 K9的三甲基修饰在这种情况下不是建立在二甲基修饰上的。此外，这些和其他数据支持这两种修饰在成年C中独立起作用的模型。线虫生殖细胞组蛋白甲基化是真核细胞染色质的一个普遍特征，与染色体功能的许多方面有关。已经注意到甲基标记出现在许多不同的氨基酸残基上，并且以不同的单甲基、二甲基和三甲基状态出现。然而，这些不同的修饰状态之间的相互作用还没有得到很好的理解。在这项工作中，我们调查的二甲基和三甲基修饰之间的关系组蛋白H3（H3 K9 me 2和H3 K9 me 3）的赖氨酸9。我们的分析利用了C。线虫生殖系，促进不同染色体特征的细胞学可视化和与不同染色质标记相关的定位的动态变化。尽管事实上H3 K9 me 2和H3 K9 me 3修饰相同的氨基酸残基，我们的工作揭示了这些标记在成体C中表现出非常不同的定位模式。elegans生殖系，并成为集中在染色质与不同的属性。此外，我们表明，这些标记是独立获得的，需要不同的组蛋白甲基转移酶，这意味着H3 K9 me 3不是建立在H3 K9 me 2标记。总的来说，我们的数据表明，H3 K9 me 2和H3 K9 me 3是高度自主的染色质修饰，在C.线虫生殖系
Histone methylation is a prominent feature of eukaryotic chromatin that modulates multiple aspects of chromosome function. Methyl modification can occur on several different amino acid residues and in distinct mono-, di-, and tri-methyl states. However, the interplay among these distinct modification states is not well understood. Here we investigate the relationships between dimethyl and trimethyl modifications on lysine 9 of histone H3 (H3K9me2 and H3K9me3) in the adult Caenorhabditis elegans germ line. Simultaneous immunofluorescence reveals very different temporal/spatial localization patterns for H3K9me2 and H3K9me3. While H3K9me2 is enriched on unpaired sex chromosomes and undergoes dynamic changes as germ cells progress through meiotic prophase, we demonstrate here that H3K9me3 is not enriched on unpaired sex chromosomes and localizes to all chromosomes in all germ cells in adult hermaphrodites and until the primary spermatocyte stage in males. Moreover, high-copy transgene arrays carrying somatic-cell specific promoters are highly enriched for H3K9me3 (but not H3K9me2) and correlate with DAPI-faint chromatin domains. We further demonstrate that the H3K9me2 and H3K9me3 marks are acquired independently. MET-2, a member of the SETDB histone methyltransferase (HMTase) family, is required for all detectable germline H3K9me2 but is dispensable for H3K9me3 in adult germ cells. Conversely, we show that the HMTase MES-2, an E(z) homolog responsible for H3K27 methylation in adult germ cells, is required for much of the germline H3K9me3 but is dispensable for H3K9me2. Phenotypic analysis of met-2 mutants indicates that MET-2 is nonessential for fertility but inhibits ectopic germ cell proliferation and contributes to the fidelity of chromosome inheritance. Our demonstration of the differential localization and independent acquisition of H3K9me2 and H3K9me3 implies that the trimethyl modification of H3K9 is not built upon the dimethyl modification in this context. Further, these and other data support a model in which these two modifications function independently in adult C. elegans germ cells. Histone methylation is a widespread feature of eukaryotic chromatin and has been implicated in numerous aspects of chromosome function. Methyl marks have been noted to occur on numerous different amino acid residues and in distinct mono-, di-, and tri-methyl states. However, the interplay among these distinct modification states is not well understood. In this work we investigate the relationships between the dimethyl and trimethyl modifications on lysine 9 of histone H3 (H3K9me2 and H3K9me3). Our analysis exploits organizational features of the C. elegans germ line that facilitate cytological visualization of distinct chromosomal features and dynamic changes in localization that are associated with different chromatin marks. Despite the fact that H3K9me2 and H3K9me3 modify the same amino acid residue, our work reveals that these marks exhibit very different localization patterns in the adult C. elegans germ line and become concentrated on chromatin with different properties. Moreover, we show that these marks are acquired independently, requiring different histone methyltransferases, implying that H3K9me3 is not built upon the H3K9me2 mark. Collectively, our data indicate that H3K9me2 and H3K9me3 are highly autonomous chromatin modifications, functioning independently of one another in the C. elegans germ line.
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影响因子：
7.7
作者：
Couteau, F;Guerry, F;Palladino, F
通讯作者：
Palladino, F
DOI：
10.1073/pnas.0406325101
发表时间：
2004-11-23
影响因子：
11.1
作者：
Khalil, AM;Boyar, FZ;Driscoll, DJ
通讯作者：
Driscoll, DJ
影响因子：
64.5
作者：
Czermin, B;Melfi, R;Pirrotta, V
通讯作者：
Pirrotta, V
影响因子：
16
作者：
Gartner, A;Milstein, S;Hengartner, MO
通讯作者：
Hengartner, MO
影响因子：
30.8
作者：
Kolasinska-Zwierz P;Down T;Latorre I;Liu T;Liu XS;Ahringer J
通讯作者：
Ahringer J