Parker J Brandon, Yin Hanwei, Vinckevicius Aurimas, Chakravarti Debabrata
Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Driskill Graduate Program in Life Sciences, Northwestern University, Chicago, IL 60611, USA.
Cell Rep. 2014 Nov 6;9(3):967-82. doi: 10.1016/j.celrep.2014.09.051. Epub 2014 Oct 30.
Host cell factor-1 (HCF-1) is a metazoan transcriptional coregulator essential for cell-cycle progression and cell proliferation. Current models suggest a mechanism whereby HCF-1 functions as a direct coregulator of E2F proteins, facilitating the expression of genes necessary for cell proliferation. In this report, we show that HCF-1 recruitment to numerous E2F-bound promoters is mediated by the concerted action of zinc finger transcription factors THAP11 and ZNF143, rather than E2F proteins directly. THAP11, ZNF143, and HCF-1 form a mutually dependent complex on chromatin, which is independent of E2F occupancy. Disruption of the THAP11/ZNF143/HCF-1 complex results in altered expression of cell-cycle control genes and leads to reduced cell proliferation, cell-cycle progression, and cell viability. These data establish a model in which a THAP11/ZNF143/HCF-1 complex is a critical component of the transcriptional regulatory network governing cell proliferation.
宿主细胞因子1（HCF-1）是一种后生动物转录共调节因子，对细胞周期进程和细胞增殖至关重要。目前的模型提出了一种机制，即HCF-1作为E2F蛋白的直接共调节因子发挥作用，促进细胞增殖所需基因的表达。在本报告中，我们表明，HCF-1被招募到众多E2F结合的启动子上是由锌指转录因子THAP11和ZNF143的协同作用介导的，而不是直接由E2F蛋白介导。THAP11、ZNF143和HCF-1在染色质上形成一个相互依赖的复合体，该复合体独立于E2F的占据情况。THAP11/ZNF143/HCF-1复合体的破坏导致细胞周期控制基因的表达改变，并导致细胞增殖、细胞周期进程和细胞活力降低。这些数据建立了一个模型，其中THAP11/ZNF143/HCF-1复合体是控制细胞增殖的转录调控网络的关键组成部分。
