Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains
Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains
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DOI：
10.1101/gr.082800.108
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发表时间：
2009-01-01
期刊：
影响因子：
7
通讯作者：
Zhao, Keji
中科院分区：
文献类型：
--
作者：
Cuddapah, Suresh;Jothi, Raja;Zhao, Keji
绝缘子是防止基因组邻近区域之间不适当相互作用的DNA元素。它们可以在功能上归类为增强子阻滞剂或域屏障。 CTCF（CCCTC结合因子）是脊椎动物中唯一已知的主要绝缘体结合蛋白，已被证明可以结合许多增强子阻断元件。但是，目前尚不清楚它是否在活性和抑制域之间的染色质结构层中起作用。在这里，我们使用CHIP-SEQ在三种细胞类型中绘制CTCF的全基因组结合位点，并确定了CTCF与H3K27me3标记的抑制性染色质结构域的边界的显着结合。尽管我们发现CTCF结合位点在三种细胞类型中的广泛重叠，但它与域边界的关联是细胞类型的特异性。我们进一步表明，CTCF结合位点侧面的核小体位置很好。有趣的是，我们发现抑制性H3K27me3和活性H2AK5AC区域之间的互补模式，这些模式被CTCF分开。我们的数据表明，CTCF可能在绝缘子的屏障活动中起重要作用，这项研究提供了一种资源，以进一步研究人类基因组中染色质的CTCF功能。
Insulators are DNA elements that prevent inappropriate interactions between the neighboring regions of the genome. They can be functionally classified as either enhancer blockers or domain barriers. CTCF ( CCCTC-binding factor) is the only known major insulator-binding protein in the vertebrates and has been shown to bind many enhancer-blocking elements. However, it is not clear whether it plays a role in chromatin domain barriers between active and repressive domains. Here, we used ChIP-seq to map the genome-wide binding sites of CTCF in three cell types and identified significant binding of CTCF to the boundaries of repressive chromatin domains marked by H3K27me3. Although we find an extensive overlapping of CTCF-binding sites across the three cell types, its association with the domain boundaries is cell-type-specific. We further show that the nucleosomes flanking CTCF-binding sites are well positioned. Interestingly, we found a complementary pattern between the repressive H3K27me3 and the active H2AK5ac regions, which are separated by CTCF. Our data indicate that CTCF may play important roles in the barrier activity of insulators, and this study provides a resource for further investigation of the CTCF function in organizing chromatin in the human genome.