Epigenetic regulation of histone H3 serine 10 phosphorylation status by HCF-1 proteins in C. elegans and mammalian cells.
Epigenetic regulation of histone H3 serine 10 phosphorylation status by HCF-1 proteins in C. elegans and mammalian cells.
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DOI：
10.1371/journal.pone.0001213
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发表时间：
2007-11-28
期刊：
影响因子：
3.7
通讯作者：
Herr, Winship
中科院分区：
文献类型：
--
作者：
Lee, Soyoung;Horn, Virginie;Julien, Eric;Liu, Yi;Wysocka, Joanna;Bowerman, Bruce;Hengartner, Michael O.;Herr, Winship
人类单纯疱疹病毒 (HSV) 宿主细胞因子 HCF-1 是一种转录共调节因子，与组蛋白甲基转移酶、乙酰转移酶以及组蛋白脱乙酰酶相关，并调节细胞增殖和分裂。在 HSV 感染的细胞中，HCF-1 与病毒蛋白 VP16 结合，促进多蛋白-DNA 转录激活复合物的形成。 HCF 蛋白稳定这种 VP16 诱导的复合物的能力在包括黑腹果蝇和秀丽隐杆线虫在内的多种动物物种中都是保守的，这表明 VP16 靶向 HCF-1 的保守细胞功能。为了研究 HCF 蛋白在动物发育中的作用，我们表征了秀丽隐杆线虫中 HCF-1 同源物（称为 Ce HCF-1）丢失的影响。两个大的 hcf-1 缺失突变体（pk924 和 ok559）是可行的，但表现出生育力降低。然而，在低温（例如 12°C）下，Ce HCF-1 蛋白的丢失会导致胚胎致死率以及早期胚胎有丝分裂和细胞分裂缺陷的高发生率，这让人想起 HCF-1 功能丧失后的哺乳动物细胞分裂缺陷。然而，即使在常温下存活，突变胚胎也会表现出磷酸组蛋白 H3 丝氨酸 10 (H3S10P) 水平降低，这是一种与转录和有丝分裂调节有关的修饰。 HCF-1 缺陷的哺乳动物细胞也表现出有丝分裂 H3S10P 状态缺陷。这些结果表明HCF-1蛋白在细胞分裂和有丝分裂组蛋白磷酸化的调节中具有保守的作用。
The human herpes simplex virus (HSV) host cell factor HCF-1 is a transcriptional coregulator that associates with both histone methyl- and acetyltransferases, and a histone deacetylase and regulates cell proliferation and division. In HSV-infected cells, HCF-1 associates with the viral protein VP16 to promote formation of a multiprotein–DNA transcriptional activator complex. The ability of HCF proteins to stabilize this VP16-induced complex has been conserved in diverse animal species including Drosophila melanogaster and Caenorhabditis elegans suggesting that VP16 targets a conserved cellular function of HCF-1. To investigate the role of HCF proteins in animal development, we have characterized the effects of loss of the HCF-1 homolog in C. elegans, called Ce HCF-1. Two large hcf-1 deletion mutants (pk924 and ok559) are viable but display reduced fertility. Loss of Ce HCF-1 protein at reduced temperatures (e.g., 12°C), however, leads to a high incidence of embryonic lethality and early embryonic mitotic and cytokinetic defects reminiscent of mammalian cell-division defects upon loss of HCF-1 function. Even when viable, however, at normal temperature, mutant embryos display reduced levels of phospho-histone H3 serine 10 (H3S10P), a modification implicated in both transcriptional and mitotic regulation. Mammalian cells with defective HCF-1 also display defects in mitotic H3S10P status. These results suggest that HCF-1 proteins possess conserved roles in the regulation of cell division and mitotic histone phosphorylation.
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