Genome-wide analysis of histone modifications in human pancreatic islets
Genome-wide analysis of histone modifications in human pancreatic islets
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DOI：
10.1101/gr.102038.109
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发表时间：
2010-04-01
期刊：
影响因子：
7
通讯作者：
Kaestner, Klaus H.
中科院分区：
文献类型：
--
作者：
Bhandare, Reena;Schug, Jonathan;Kaestner, Klaus H.
全球糖尿病流行构成了一个重大挑战。表观遗传事件有助于糖尿病的病因学，然而，缺乏表观基因组分析限制了阐明这种联系的机制基础。为了确定人类胰岛的表观遗传结构，我们绘制了四个组蛋白标记的全基因组位置：三个与基因激活相关-H3 K4 me 1，H3 K4 me 2和H3 K4 me 3-以及一个与基因抑制相关，H3 K27 me 3。有趣的是，高度转录的胰岛素和胰高血糖素基因的启动子仅稀疏地被H3 K4 me 2和H3 K4 me 3占据。在全球范围内，我们确定了启动子结构，组蛋白修饰和基因表达之间的重要关系。我们证明了成熟胰岛中组蛋白修饰（包括二价标记）的共同发生。此外，我们发现了一组启动子，在胰岛和其他细胞类型之间差异修饰。我们还使用组蛋白标记来确定哪些已知的糖尿病相关单核苷酸多态性可能是调节元件的一部分。我们的全球组蛋白标记图谱将成为了解2型糖尿病表观遗传基础的重要资源。
The global diabetes epidemic poses a major challenge. Epigenetic events contribute to the etiology of diabetes; however, the lack of epigenomic analysis has limited the elucidation of the mechanistic basis for this link. To determine the epigenetic architecture of human pancreatic islets we mapped the genome-wide locations of four histone marks: three associated with gene activation-H3K4me1, H3K4me2, and H3K4me3-and one associated with gene repression, H3K27me3. Interestingly, the promoters of the highly transcribed insulin and glucagon genes are occupied only sparsely by H3K4me2 and H3K4me3. Globally, we identified important relationships between promoter structure, histone modification, and gene expression. We demonstrated co-occurrences of histone modifications including bivalent marks in mature islets. Furthermore, we found a set of promoters that is differentially modified between islets and other cell types. We also use our histone marks to determine which of the known diabetes-associated single-nucleotide polymorphisms are likely to be part of regulatory elements. Our global map of histone marks will serve as an important resource for understanding the epigenetic basis of type 2 diabetes.