Reduction of Hox gene expression by histone H1 depletion.
Reduction of Hox gene expression by histone H1 depletion.
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DOI：
10.1371/journal.pone.0038829
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fan Y
中科院分区：
文献类型：
--
作者：
Zhang Y;Liu Z;Medrzycki M;Cao K;Fan Y
进化上保守的同源异型(Hox)基因被组织成簇，并共线表达，以指定胚胎发育期间的身体模式。染色质的重组和解压与HOX基因的激活密切相关。连接子组蛋白H1在促进高阶染色质结构的折叠中起着关键作用。以往的研究表明，三种体细胞H1亚型的缺失共同导致胚胎死亡，并且H1c/H1d/H1e三重敲除(TKO)的胚胎干细胞(ESCs)表现出大量的染色质分解。为了探讨H1和高阶染色质折叠在HOX基因表达调控中的潜在作用，我们用定量RT-PCR方法系统地分析了所有39个HOX基因在三个H1缺失的小鼠胚胎和ESCs中的表达。令人惊讶的是，我们发现H1的缺失导致胚胎和ESCs中一系列HOX基因的表达显著减少。为了研究三种H1亚型(H1c、H1d和H1e)中的任何一种是否与三重H1缺失ESCs中HOX基因的表达降低有关，我们衍生并鉴定了H1c−/−、H1d−/−和H1e−/−Single-H1缺失ESCs。我们发现，个别H1亚型的缺失会导致ESCs中特定的HOX基因下调。最后，我们证明，在三个H1缺失和单个H1缺失的ESCs中，H3K4三甲基化(H3K4me3)和H3K27三甲基化(H3K27me3)的水平在特定的Hox基因上受到影响，表达降低。我们的数据表明，总H1水平的显著降低导致许多HOX基因的活化组蛋白标记H3K4me3的表达和水平显著降低，个别H1亚型也可能参与特定HOX基因表达的调节。我们提出了组蛋白H1在HOX基因调控中出人意料的作用的可能机制。
The evolutionarily conserved homeotic (Hox) genes are organized in clusters and expressed collinearly to specify body patterning during embryonic development. Chromatin reorganization and decompaction are intimately connected with Hox gene activation. Linker histone H1 plays a key role in facilitating folding of higher order chromatin structure. Previous studies have shown that deletion of three somatic H1 subtypes together leads to embryonic lethality and that H1c/H1d/H1e triple knockout (TKO) embryonic stem cells (ESCs) display bulk chromatin decompaction. To investigate the potential role of H1 and higher order chromatin folding in the regulation of Hox gene expression, we systematically analyzed the expression of all 39 Hox genes in triple H1 null mouse embryos and ESCs by quantitative RT-PCR. Surprisingly, we find that H1 depletion causes significant reduction in the expression of a broad range of Hox genes in embryos and ESCs. To examine if any of the three H1 subtypes (H1c, H1d and H1e) is responsible for decreased expression of Hox gene in triple-H1 null ESCs, we derived and characterized H1c−/−, H1d−/−, and H1e−/− single-H1 null ESCs. We show that deletion of individual H1 subtypes results in down-regulation of specific Hox genes in ESCs. Finally we demonstrate that, in triple-H1- and single-H1- null ESCs, the levels of H3K4 trimethylation (H3K4me3) and H3K27 trimethylation (H3K27me3) were affected at specific Hox genes with decreased expression. Our data demonstrate that marked reduction in total H1 levels causes significant reduction in both expression and the level of active histone mark H3K4me3 at many Hox genes and that individual H1 subtypes may also contribute to the regulation of specific Hox gene expression. We suggest possible mechanisms for such an unexpected role of histone H1 in Hox gene regulation.
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影响因子：
5.2
作者：
Gouti, Mina;Gavalas, Anthony
通讯作者：
Gavalas, Anthony
影响因子：
5.3
作者：
Fan, YH;Nikitina, T;Skoultchi, AI
通讯作者：
Skoultchi, AI
影响因子：
34.7
作者：
Erzurumlu, Reha S.;Murakami, Yasunori;Rijli, Filippo M.
通讯作者：
Rijli, Filippo M.
DOI：
10.1002/ajmg.10776
发表时间：
2002-10-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Goodman, FR
通讯作者：
Goodman, FR
影响因子：
64.5
作者：
Christensen, Jesper;Agger, Karl;Helin, Kristian
通讯作者：
Helin, Kristian