Freddie Cecilie T, Ji Zongling, Marais Anett, Sharrocks Andrew D
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK.
Nucleic Acids Res. 2007;35(15):5203-12. doi: 10.1093/nar/gkm528. Epub 2007 Aug 1.
The combinatorial control of gene expression by the association of members of different families of transcription factors is a common theme in eukaryotic transcriptional control. The MADS-box transcription factors SRF and Mcm1 represent paradigms for such regulation through their interaction with numerous partner proteins. For example, in Saccharomyces cerevisiae, Mcm1 interacts with the forkhead transcription factor Fkh2. Here, we identify a novel interaction between SRF and the Forkhead transcription factor FOXK1 in human cells. The importance of this interaction is shown for the regulation of the SRF target genes SM alpha-actin and PPGB. The binding of FOXK1 to the SM alpha-actin and PPGB promoters requires the presence of SRF on the promoter. FOXK1 acts as a transcriptional repressor and it represses SM alpha-actin and PPGB expression. Thus FOXK1 represents an additional member of the growing repertoire of transcription factors that can interact with SRF and modulate the transcriptional output from SRF-regulated promoters.
不同家族转录因子成员通过相互作用对基因表达进行组合调控是真核生物转录调控中的一个常见主题。MADS盒转录因子SRF和Mcm1通过与众多伴侣蛋白相互作用，成为这种调控的范例。例如，在酿酒酵母中，Mcm1与叉头转录因子Fkh2相互作用。在此，我们在人类细胞中鉴定出SRF与叉头转录因子FOXK1之间的新型相互作用。这种相互作用对SRF靶基因SMα-肌动蛋白和PPGB的调控作用得以展现。FOXK1与SMα-肌动蛋白和PPGB启动子的结合需要启动子上存在SRF。FOXK1作为转录抑制因子，抑制SMα-肌动蛋白和PPGB的表达。因此，FOXK1是不断增加的能够与SRF相互作用并调节SRF调控启动子转录输出的转录因子库中的又一成员。
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