由RYBP介导的YY1与E2Fs的相互作用为E2F功能的特异性提供了一种机制。
Interaction of YY1 with E2Fs, mediated by RYBP, provides a mechanism for specificity of E2F function.
作者信息
Schlisio Susanne, Halperin Terri, Vidal Miguel, Nevins Joseph R
机构信息
Department of Molecular Genetics and Microbiology and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
出版信息
EMBO J. 2002 Nov 1;21(21):5775-86. doi: 10.1093/emboj/cdf577.
To explore mechanisms for specificity of function within the family of E2F transcription factors, we have identified proteins that interact with individual E2F proteins. A two-hybrid screen identified RYBP (Ring1- and YY1-binding protein) as a protein that interacts specifically with the E2F2 and E2F3 family members, dependent on the marked box domain in these proteins. The Cdc6 promoter contains adjacent E2F- and YY1-binding sites, and both are required for promoter activity. In addition, YY1 and RYBP, in combination with either E2F2 or E2F3, can stimulate Cdc6 promoter activity synergistically, dependent on the marked box domain of E2F3. Using chromatin immunoprecipitation assays, we show that both E2F2 and E2F3, as well as YY1 and RYBP, associate with the Cdc6 promoter at G(1)/S of the cell cycle. In contrast, we detect no interaction of E2F1 with the Cdc6 promoter. We suggest that the ability of RYBP to mediate an interaction between E2F2 or E2F3 and YY1 is an important component of Cdc6 activation and provides a basis for specificity of E2F function.
为了探究E2F转录因子家族中功能特异性的机制，我们鉴定了与单个E2F蛋白相互作用的蛋白质。一项双杂交筛选确定RYBP（Ring1和YY1结合蛋白）是一种依赖于这些蛋白中的标记框结构域而与E2F2和E2F3家族成员特异性相互作用的蛋白质。Cdc6启动子含有相邻的E2F结合位点和YY1结合位点，两者都是启动子活性所必需的。此外，YY1和RYBP与E2F2或E2F3结合时，可协同刺激Cdc6启动子活性，这依赖于E2F3的标记框结构域。通过染色质免疫沉淀试验，我们发现E2F2和E2F3以及YY1和RYBP在细胞周期的G(1)/S期与Cdc6启动子结合。相比之下，我们未检测到E2F1与Cdc6启动子之间的相互作用。我们认为，RYBP介导E2F2或E2F3与YY1之间相互作用的能力是Cdc6激活的一个重要组成部分，并为E2F功能的特异性提供了基础。
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