The binding sites for the chromatin insulator protein CTCF map to DNA methylation-free domains genome-wide
The binding sites for the chromatin insulator protein CTCF map to DNA methylation-free domains genome-wide
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DOI：
10.1101/gr.2408304
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发表时间：
2004-08-01
期刊：
影响因子：
7
通讯作者：
Ohlsson, R
中科院分区：
文献类型：
--
作者：
Mukhopadhyay, R;Yu, WQ;Ohlsson, R
所有已知的脊椎动物染色质绝缘体都与高度保守的多价ii -锌指核因子CTCF相互作用，以位置依赖的方式阻断增强子或沉默子信号，从而划定表达域。最近的观察表明，CTCF的特性包括读取和传播差异甲基化H19印迹控制区的表观遗传状态。为了评估这些发现是否反映了CTCF靶点的普遍作用，我们通过生成染色质免疫纯化（ChIP） DNA克隆的DNA微阵列，然后进行ChIP-on- ChIP杂交分析，确定了200多个新的CTCF靶点。靶点不仅包括已知的涉及多种细胞功能的位点，如代谢、神经发生、生长、凋亡和信号传导，还可能包括异染色质序列。利用一种新的绝缘子捕获试验，我们还表明，大多数这些目标具有连续分布的严格绝缘子功能。由于这些靶点通常是DNA甲基化的，通过针对5-甲基胞苷和甲基结合蛋白（MBD2）的抗体确定，基于ctcf的网络与全基因组表观遗传状态相关。
All known vertebrate chromatin insulators interact with the highly conserved, multivalent II-zinc finger nuclear factor CTCF to demarcate expression domains by blocking enhancer or silencer signals in a position-dependent manner. Recent observations document that the properties of CTCF include reading and propagating the epigenetic state of the differentially methylated H19 imprinting control region. To assess whether these findings may reflect a universal role for CTCF targets, we identified more than 200 new CTCF target sites by generating DNA microarrays of clones derived from chromatin-immunopurified (ChIP) DNA followed by ChIP-on-chip hybridization analysis. Target sites include not only known loci involved in multiple cellular functions, Such as metabolism, neurogenesis, growth, apoptosis, and signalling, but potentially also heterochromatic sequences. Using a novel insulator trapping assay, we also show that the majority of these targets manifest insulator functions with a continuous distribution of stringency. As these targets are generally DNA methylation-free as determined by antibodies against 5-methylcytidine and a methyl-binding protein (MBD2), a CTCF-based network correlates with genome-wide epigenetic states.