Dale Rodney M, Remo Benjamin F, Svensson Eric C
Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC6088, Chicago, IL 60637, USA.
Biochem Biophys Res Commun. 2007 Jun 8;357(3):683-7. doi: 10.1016/j.bbrc.2007.04.008. Epub 2007 Apr 10.
The FOG family of transcriptional co-factors is composed of two members in mammals: FOG-1 and FOG-2. Both have been shown to bind to GATA factors and function as transcriptional co-repressors in specific cell and promoter contexts. We have previously defined a novel repression domain localized to the N-terminus of each FOG family member, the FOG repression motif, which is necessary for FOG-mediated transcriptional repression. In this report, we describe the identification and characterization of a novel isoform of FOG-2 lacking the FOG repression motif. In contrast to full-length FOG-2, this isoform is expressed predominately in the embryonic and adult heart. It can bind GATA4 avidly, but is unable to repress GATA4-mediated activation of cardiac-restricted gene promoters. Together, these results suggest that FOG-2 repressive activity may be modulated by the generation of isoforms of FOG-2 lacking the FOG repression motif.
转录辅因子FOG家族在哺乳动物中由两个成员组成:FOG-1和FOG-2。二者均已被证明可与GATA因子结合,并在特定细胞和启动子环境中作为转录共抑制因子发挥作用。我们之前确定了一个位于每个FOG家族成员N端的新型抑制结构域,即FOG抑制基序,它是FOG介导的转录抑制所必需的。在本报告中,我们描述了一种缺乏FOG抑制基序的新型FOG-2异构体的鉴定和特征。与全长FOG-2相反,这种异构体主要在胚胎和成年心脏中表达。它能与GATA4紧密结合,但无法抑制GATA4介导的心脏限制性基因启动子的激活。这些结果共同表明,FOG-2的抑制活性可能通过缺乏FOG抑制基序的FOG-2异构体的产生而受到调节。