Local chromatin dynamics of transcription factors imply cell-lineage specific functions during cellular differentiation.

Local chromatin dynamics of transcription factors imply cell-lineage specific functions during cellular differentiation.
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转录因子的局部染色质动态暗示细胞分化过程中的细胞谱系特异性功能

DOI:
10.4161/epi.7.1.18683
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发表时间:
2012-01-01
期刊:
影响因子:
3.7
通讯作者:
Zhang Y
Zhang Y
中科院分区:
生物学3区
文献类型:
--
作者:
Tian R;Feng J;Cai X;Zhang Y

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细胞分化状态的染色质动力学是一个新兴的观点,从全球基因表达调控的机制可能会更好地理解。虽然一些组蛋白标记的作用已经部分解释了它们与基因转录的关系,但从基因座特异性的角度来看,组蛋白标记在细胞分化过程中的动力学还没有得到很好的研究。我们建立了一种方法,系统地评估组蛋白修饰的基因在不同的细胞分化状态的变化。我们计算了人类血细胞分化过程中超过1300种策划的转录因子(TF)的H3K4me3,H3K27me3和H3K36me3的组蛋白修饰变异评分。造血特异性TF(通过文献挖掘确定)被具有较高组蛋白修饰变异评分的TF显著过度代表。基于组蛋白修饰变异评分的所有TF的分层聚类定义了一组TF,其中已知或潜在的造血特异性TF显著富集。我们的研究结果表明,跨细胞分化状态的转录因子的局部染色质状态动态可能意味着细胞系特异性功能。更重要的是,我们的方法可以应用于更广泛的系统,持有的承诺,发现从头,谱系特异性的TF通过询问他们的组蛋白修饰动力学跨细胞谱系。
Chromatin dynamics across cellular differentiation states is an emerging perspective from which the mechanism of global gene expression regulation may be better understood. While the roles of some histone marks have been partially interpreted in terms of their association with gene transcription, the dynamics of histone marks from a loci-specific perspective during cellular differentiation is not well studied. We established a method to systematically assess the histone modification variations of genes across various cellular differentiation states. We calculated the histone modification variation scores of H3K4me3, H3K27me3 and H3K36me3 for over 1300 curated transcription factors (TFs) during human blood cell differentiation. Hematopoietic-specific TFs (identified by literature mining) were significantly overrepresented by TFs with higher histone modification variation scores. Hierarchical clustering of all TFs based on the histone modification variation scores defined a group of TFs where known or potential hematopoietic-specific TFs were remarkably enriched. Our results suggest that local chromatin state dynamics of transcription factors across cellular differentiation states could imply cell lineage-specific functions. More importantly, our method can be applied to broader systems, holding the promise to discover de novo, lineage-specific TFs by interrogating their histone modification dynamics across cell lineages.
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