CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features.
CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features.
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DOI：
10.1186/gb-2009-10-11-r131
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发表时间：
2009
期刊：
影响因子：
12.3
通讯作者：
Hannenhalli S
中科院分区：
文献类型：
--
作者：
Essien K;Vigneau S;Apreleva S;Singh LN;Bartolomei MS;Hannenhalli S
CTCF DNA结合位点被分为不同的功能类别，具有不同的生物学特性，揭示了CTCF结合的不同功能作用。CTCF（CCCTC结合因子）是一种进化上保守的锌指蛋白，参与多种功能，从MYC的负调控，到β-珠蛋白基因簇的染色质绝缘，再到Igf 2基因座的印记。已知CTCF的11个锌指在不同结合位点对CTCF-DNA相互作用有不同贡献。这可能是由于CTCF-DNA在不同结合位点的构象差异导致了CTCF的功能多样性。如果是这样，CTCF结合位点可能属于不同的类别，每个类别与特定的功能作用相容。我们已经将CD 4 + T细胞中约26，000个CTCF结合位点根据其与充分表征的CTCF DNA结合基序的相似性分为三类。我们已经全面的特点，这三类CTCF网站方面的几个进化，基因组，表观基因组，转录和功能的特点。我们发现，低占有率的网站往往是细胞类型的具体。此外，虽然高占有率位点与抑制性组蛋白标记和CTCF侧翼区块内更高的基因共表达相关，但低占有率位点与活性组蛋白标记和更高的基因表达相关。我们发现，低占用率的网站有更大的保护，在其侧翼地区相比，高占用率的网站。有趣的是，基于一种新的类保守性度量，我们观察到人类低占用位点倾向于比预期更频繁地被保守为小鼠中的低占用位点（反之亦然）。我们的工作揭示了几个关键的差异CTCF占用率为基础的类，并提出了一个关键的，但独特的功能作用低占用率的网站。
CTCF DNA binding sites are classified into distinct functional classes, with distinct biological properties, shedding light on the differing functional roles of CTCF binding. CTCF (CCCTC-binding factor) is an evolutionarily conserved zinc finger protein involved in diverse functions ranging from negative regulation of MYC, to chromatin insulation of the beta-globin gene cluster, to imprinting of the Igf2 locus. The 11 zinc fingers of CTCF are known to differentially contribute to the CTCF-DNA interaction at different binding sites. It is possible that the differences in CTCF-DNA conformation at different binding sites underlie CTCF's functional diversity. If so, the CTCF binding sites may belong to distinct classes, each compatible with a specific functional role. We have classified approximately 26,000 CTCF binding sites in CD4+ T cells into three classes based on their similarity to the well-characterized CTCF DNA-binding motif. We have comprehensively characterized these three classes of CTCF sites with respect to several evolutionary, genomic, epigenomic, transcriptomic and functional features. We find that the low-occupancy sites tend to be cell type specific. Furthermore, while the high-occupancy sites associate with repressive histone marks and greater gene co-expression within a CTCF-flanked block, the low-occupancy sites associate with active histone marks and higher gene expression. We found that the low-occupancy sites have greater conservation in their flanking regions compared to high-occupancy sites. Interestingly, based on a novel class-conservation metric, we observed that human low-occupancy sites tend to be conserved as low-occupancy sites in mouse (and vice versa) more frequently than expected. Our work reveals several key differences among CTCF occupancy-based classes and suggests a critical, yet distinct functional role played by low-occupancy sites.