Transcriptional repression of Hox genes by C. elegans HP1/HPL and H1/HIS-24.
Transcriptional repression of Hox genes by C. elegans HP1/HPL and H1/HIS-24.
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DOI：
10.1371/journal.pgen.1002940
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发表时间：
2012-09
期刊：
影响因子：
4.5
通讯作者：
Jedrusik-Bode M
中科院分区：
文献类型：
--
作者：
Studencka M;Wesołowski R;Opitz L;Salinas-Riester G;Wisniewski JR;Jedrusik-Bode M
由于在小鼠中存在至少11个不同的组蛋白和3个亚型，因此很难阐明连接蛋白(H1)和异染色质蛋白1(HP1)在哺乳动物中的生物学作用。秀丽线虫具有两个HP1同源物(HPL-1和HPL-2)和八个H1变异体。值得注意的是，8个H1变种之一His-24对线虫的发育很重要。因此，我们决定平行分析His-24、HPL-1/-2缺陷动物的转录图谱及其表型，因为HPL-1、HPL-2和His-24缺陷线虫是活的。对两个和三个突变体的全局转录分析表明，HPL蛋白和His-24发挥基因特异性作用，而不是一般的抑制功能。我们发现His-24与HPL协同作用，允许正常生殖、体细胞性腺发育和外阴细胞命运决定。此外，Hpl-2；His-24双突变动物雄性尾部发育异常，线虫Hom-C/Hox基因(EGL-5和MAB-5)异位表达，参与雄性交配结构的发育模式。我们发现HPL-2和His-24的甲基化形式在三甲基化状态下与组蛋白H3K27区域特异地相互作用，His-24与EGL-5和mab-5基因相关联。我们的结果建立了HPL-1/-2和His-24蛋白在调节雄性线虫位置认同方面的相互作用。连接物组蛋白(H1)和异染色质蛋白1(HP1)在高阶染色质结构的形成和基因表达中起着核心作用。最近的研究表明，H1和HP1之间存在物理相互作用；然而，组蛋白H1和HP1的生物学作用尚不清楚。此外，HP1和H1亚型相互作用在任何生物体中的功能还没有被解决，主要是由于缺乏基因敲除等位基因。在这里，我们以线虫为模型系统，研究HP1和H1在发育中的作用。我们着重于H1和HP1基因共同调控的潜在分子机制。我们发现HP1和H1的缺失改变了一小部分基因的表达。线虫HP1和H1在相同或平行的途径上具有重叠的功能，在这些途径中，它们调节共同的靶标-HOX基因。
Elucidation of the biological role of linker histone (H1) and heterochromatin protein 1 (HP1) in mammals has been difficult owing to the existence of a least 11 distinct H1 and three HP1 subtypes in mice. Caenorhabditis elegans possesses two HP1 homologues (HPL-1 and HPL-2) and eight H1 variants. Remarkably, one of eight H1 variants, HIS-24, is important for C. elegans development. Therefore we decided to analyse in parallel the transcriptional profiles of HIS-24, HPL-1/-2 deficient animals, and their phenotype, since hpl-1, hpl-2, and his-24 deficient nematodes are viable. Global transcriptional analysis of the double and triple mutants revealed that HPL proteins and HIS-24 play gene-specific roles, rather than a general repressive function. We showed that HIS-24 acts synergistically with HPL to allow normal reproduction, somatic gonad development, and vulval cell fate decision. Furthermore, the hpl-2; his-24 double mutant animals displayed abnormal development of the male tail and ectopic expression of C. elegans HOM-C/Hox genes (egl-5 and mab-5), which are involved in the developmental patterning of male mating structures. We found that HPL-2 and the methylated form of HIS-24 specifically interact with the histone H3 K27 region in the trimethylated state, and HIS-24 associates with the egl-5 and mab-5 genes. Our results establish the interplay between HPL-1/-2 and HIS-24 proteins in the regulation of positional identity in C. elegans males. Linker histone (H1) and heterochromatin protein 1 (HP1) play central roles in the formation of higher-order chromatin structure and gene expression. Recent studies have shown a physical interaction between H1 and HP1; however, the biological role of histone H1 and HP1 is not well understood. Additionally, the function of HP1 and H1 isoform interactions in any organism has not been addressed, mostly due to the lack of knockout alleles. Here, we investigate the role of HP1 and H1 in development using the nematode C. elegans as a model system. We focus on the underlying molecular mechanisms of gene co-regulation by H1 and HP1. We show that the loss of both HP1 and H1 alters the expression of a small subset of genes. C. elegans HP1 and H1 have an overlapping function in the same or parallel pathways where they regulate a shared target, the Hox genes.
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