Voth Warren P, Yu Yaxin, Takahata Shinya, Kretschmann Kelsi L, Lieb Jason D, Parker Rebecca L, Milash Brett, Stillman David J
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
EMBO J. 2007 Oct 17;26(20):4324-34. doi: 10.1038/sj.emboj.7601859. Epub 2007 Sep 27.
Transcription factors with identical DNA-binding specificity often activate different genes in vivo. Yeast Ace2 and Swi5 are such activators, with targets we classify as Swi5-only, Ace2-only, or both. We define two unique regulatory modes. Ace2 and Swi5 both bind in vitro to Swi5-only genes such as HO, but only Swi5 binds and activates in vivo. In contrast, Ace2 and Swi5 both bind in vivo to Ace2-only genes, such as CTS1, but promoter-bound Swi5 fails to activate. We show that activation by Swi5 is prevented by the binding of the Forkhead factors Fkh1 and Fkh2, which recruit the Rpd3(Large) histone deacetylase complex to the CTS1 promoter. Global analysis shows that all Ace2-only genes are bound by both Ace2 and Swi5, and also by Fkh1/2. Genes normally activated by either Ace2 or Swi5 can be converted to Ace2-only genes by the insertion of Fkh-binding sites. Thus Fkh proteins, which function initially to activate SWI5 and ACE2, subsequently function as Swi5-specific antiactivators.
具有相同DNA结合特异性的转录因子在体内通常会激活不同的基因。酵母Ace2和Swi5就是这样的激活因子，其靶标我们分为仅Swi5、仅Ace2或两者兼具。我们定义了两种独特的调控模式。Ace2和Swi5在体外均与仅Swi5的基因（如HO）结合，但在体内只有Swi5结合并激活。相反，Ace2和Swi5在体内均与仅Ace2的基因（如CTS1）结合，但与启动子结合的Swi5无法激活。我们发现，叉头因子Fkh1和Fkh2的结合会阻止Swi5的激活，它们会将Rpd3（Large）组蛋白去乙酰化酶复合物招募到CTS1启动子上。全局分析表明，所有仅Ace2的基因都被Ace2和Swi5以及Fkh1/2结合。通过插入Fkh结合位点，通常由Ace2或Swi5激活的基因可以转化为仅Ace2的基因。因此，最初起激活SWI5和ACE2作用的Fkh蛋白，随后作为Swi5特异性的抗激活因子发挥作用。
