Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, México D.F. 04510, México.
Biochem Cell Biol. 2011 Oct;89(5):479-88. doi: 10.1139/o11-031. Epub 2011 Aug 17.
One of the most outstanding nuclear factors, which has chromatin insulator and transcriptional properties and also contribute to genomic organization, is the zinc-finger protein CCCTC-binding factor (CTCF). Among its multiple functions, a growing amount of evidence implicates CTCF in the epigenetic regulation of genes responsible for the control of the cell cycle, and its mis-regulation can lead to aberrant epigenetic silencing of genes involved in cancer development. Detailed studies are now revealing that CTCF can serve as a barrier against the spread of DNA methylation and histone repressive marks over promoter regions of tumor suppressor genes. Moreover, new evidences points out to the capacity of CTCF to be covalently modified, in particular, through poly(ADP-ribosyl)ation with regulatory consequences. An unexplored aspect of CTCF is its intergenic and intragenic distribution in certain loci. Such distribution seems to facilitate the formation of an optimal chromatin structure and the recruitment of chromatin remodelers with the possible incorporation of RNA polymerase II. Therefore, in the context of tumor suppressor genes and cancer development, CTCF appears to play a relevant role by incorporating a combination of mechanisms involved in the protection against epigenetic silencing components and the maintenance of optimal higher-order organization of the corresponding loci.
其中一个最为突出的核因子是锌指蛋白 CCCTC 结合因子（CTCF），它具有染色质绝缘子和转录性质，并有助于基因组组织。在其多种功能中，越来越多的证据表明 CTCF 参与了控制细胞周期的基因的表观遗传调控，其调控失常可导致参与癌症发展的基因出现异常的表观遗传沉默。目前的详细研究揭示了 CTCF 可以作为阻止 DNA 甲基化和组蛋白抑制标记在肿瘤抑制基因启动子区域扩散的障碍。此外，新的证据指出 CTCF 具有共价修饰的能力，特别是通过多聚（ADP-核糖基）化进行修饰，并具有调节作用。CTCF 在某些基因座中的基因间和基因内分布是一个尚未被探索的方面。这种分布似乎有利于形成最佳染色质结构，并招募染色质重塑因子，可能包括 RNA 聚合酶 II。因此，在肿瘤抑制基因和癌症发展的背景下，CTCF 通过整合涉及保护免受表观遗传沉默成分和维持相应基因座的最佳高级组织的多种机制，似乎发挥了相关作用。
