Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China.
PLoS One. 2012;7(7):e41374. doi: 10.1371/journal.pone.0041374. Epub 2012 Jul 19.
Chromatin insulators are DNA elements that regulate the level of gene expression either by preventing gene silencing through the maintenance of heterochromatin boundaries or by preventing gene activation by blocking interactions between enhancers and promoters. CCCTC-binding factor (CTCF), a ubiquitously expressed 11-zinc-finger DNA-binding protein, is the only protein implicated in the establishment of insulators in vertebrates. While CTCF has been implicated in diverse regulatory functions, CTCF has only been studied in a limited number of cell types across human genome. Thus, it is not clear whether the identified cell type-specific differences in CTCF-binding sites are functionally significant. Here, we identify and characterize cell type-specific and ubiquitous CTCF-binding sites in the human genome across 38 cell types designated by the Encyclopedia of DNA Elements (ENCODE) consortium. These cell type-specific and ubiquitous CTCF-binding sites show uniquely versatile transcriptional functions and characteristic chromatin features. In addition, we confirm the insulator barrier function of CTCF-binding and explore the novel function of CTCF in DNA replication. These results represent a critical step toward the comprehensive and systematic understanding of CTCF-dependent insulators and their versatile roles in the human genome.
染色质绝缘子是调节基因表达水平的 DNA 元件，其通过维持异染色质边界防止基因沉默，或者通过阻止增强子和启动子之间的相互作用来防止基因激活。CCCTC 结合因子（CTCF）是一种广泛表达的 11 个锌指 DNA 结合蛋白，是唯一一种在脊椎动物中被认为与绝缘子的形成有关的蛋白质。虽然 CTCF 被认为具有多种调节功能，但在人类基因组中仅在有限数量的细胞类型中对 CTCF 进行了研究。因此，尚不清楚鉴定的 CTCF 结合位点的细胞类型特异性差异是否具有功能意义。在这里，我们在 38 种由 DNA 元件百科全书（ENCODE）联盟指定的细胞类型中鉴定和表征了人类基因组中的细胞类型特异性和普遍存在的 CTCF 结合位点。这些细胞类型特异性和普遍存在的 CTCF 结合位点显示出独特的多功能转录功能和特征性染色质特征。此外，我们还证实了 CTCF 结合的绝缘子屏障功能，并探索了 CTCF 在 DNA 复制中的新功能。这些结果是朝着全面系统地理解 CTCF 依赖性绝缘子及其在人类基因组中的多功能作用迈出的关键一步。
