Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada.
BMC Biol. 2010 Jul 30;8:105. doi: 10.1186/1741-7007-8-105.
CTCF is a versatile zinc finger DNA-binding protein that functions as a highly conserved epigenetic transcriptional regulator. CTCF is known to act as a chromosomal insulator, bind promoter regions, and facilitate long-range chromatin interactions. In mammals, CTCF is active in the regulatory regions of some genes that exhibit genomic imprinting, acting as insulator on only one parental allele to facilitate parent-specific expression. In Drosophila, CTCF acts as a chromatin insulator and is thought to be actively involved in the global organization of the genome.
To determine whether CTCF regulates imprinting in Drosophila, we generated CTCF mutant alleles and assayed gene expression from the imprinted Dp(1;f)LJ9 mini-X chromosome in the presence of reduced CTCF expression. We observed disruption of the maternal imprint when CTCF levels were reduced, but no effect was observed on the paternal imprint. The effect was restricted to maintenance of the imprint and was specific for the Dp(1;f)LJ9 mini-X chromosome.
CTCF in Drosophila functions in maintaining parent-specific expression from an imprinted domain as it does in mammals. We propose that Drosophila CTCF maintains an insulator boundary on the maternal X chromosome, shielding genes from the imprint-induced silencing that occurs on the paternally inherited X chromosome. See commentary: http://www.biomedcentral.com/1741-7007/8/104.
CTCF 是一种多功能锌指 DNA 结合蛋白,作为高度保守的表观遗传转录调节剂发挥作用。CTCF 已知作为染色体绝缘子,结合启动子区域,并促进长距离染色质相互作用。在哺乳动物中,CTCF 在表现基因组印记的一些基因的调控区域中活跃,仅在一个亲本等位基因上作为绝缘子起作用,以促进亲本特异性表达。在果蝇中,CTCF 作为染色质绝缘子起作用,并且被认为积极参与基因组的全局组织。
为了确定 CTCF 是否在果蝇中调节印迹,我们生成了 CTCF 突变等位基因,并在降低 CTCF 表达的情况下检测印迹的 Dp(1;f)LJ9 小型 X 染色体上基因的表达。当 CTCF 水平降低时,我们观察到母体印迹的破坏,但对父体印迹没有影响。这种影响仅限于印迹的维持,并且仅限于 Dp(1;f)LJ9 小型 X 染色体。
果蝇中的 CTCF 与在哺乳动物中一样,在维持印迹区域的亲本特异性表达方面发挥作用。我们提出,果蝇 CTCF 在母体 X 染色体上维持一个绝缘子边界,使基因免受在父本遗传的 X 染色体上发生的印迹诱导沉默的影响。参见评论:http://www.biomedcentral.com/1741-7007/8/104。