H3K4me3 breadth is linked to cell identity and transcriptional consistency.
H3K4me3 breadth is linked to cell identity and transcriptional consistency.
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DOI：
10.1016/j.cell.2014.06.027
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发表时间：
2014-07-31
期刊：
影响因子：
64.5
通讯作者：
Brunet A
中科院分区：
文献类型：
--
作者：
Benayoun BA;Pollina EA;Ucar D;Mahmoudi S;Karra K;Wong ED;Devarajan K;Daugherty AC;Kundaje AB;Mancini E;Hitz BC;Gupta R;Rando TA;Baker JC;Snyder MP;Cherry JM;Brunet A
组蛋白H3在赖氨酸4位点的三甲基化（H3K4me3）是一种已知的染色质修饰，可以标记活性基因的转录起始位点。在这里，我们发现H3K4me3结构域在特定细胞类型的基因上更广泛地分布，优先标记对该细胞类型的身份和功能至关重要的基因。利用最广泛的H3K4me3结构域作为神经祖细胞的发现工具，我们确定了这些细胞的新调节因子。机器学习模型显示，最宽的H3K4me3结构域代表一个独特的实体，其特征是伸长的标记增加。最宽的H3K4me3结构域在其启动子处也有更多的暂停聚合酶，这表明它具有独特的转录输出。事实上，由最宽的H3K4me3结构域标记的基因表现出增强的转录一致性，而不是增加的转录水平，并且H3K4me3宽度的扰动导致转录一致性的变化。因此，H3K4me3宽度包含的信息可以确保关键细胞身份/功能基因的转录精度。
Trimethylation of Histone H3 at Lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here we show that H3K4me3 domains that spread more broadly over genes in a given cell type preferentially mark genes essential for the identity and function of that cell type. Using the broadest H3K4me3 domains as a discovery tool in neural progenitor cells, we identify novel regulators of these cells. Machine learning models reveal that the broadest H3K4me3 domains represent a distinct entity, characterized by increased marks of elongation. Broadest H3K4me3 domains also have more paused polymerase at their promoters, suggesting a unique transcriptional output. Indeed, genes marked by broadest H3K4me3 domains exhibit enhanced transcriptional consistency rather than increased transcriptional levels, and perturbation of H3K4me3 breadth leads to changes in transcriptional consistency. Thus, H3K4me3 breadth contains information that could ensure transcriptional precision at key cell identity/function genes.
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