Open AccessKlf4 Cooperates with Oct3/4 and Sox2 To Activate the Lefty1 Core Promoter in Embryonic Stem Cells
Author(s) -
Yuhki Nakatake,
Nobutaka Fukui,
Yuko Iwamatsu,
Shinji Masui,
Kadue Takahashi,
Rika Yagi,
Kiyohito Yagi,
Junichi Miyazaki,
Ryo Matoba,
Minoru S.H. Ko,
Hitoshi Niwa
Publication year - 2006
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00468-06
Subject(s) - sox2 , pou domain , biology , klf4 , enhancer , transcription factor , transactivation , embryonic stem cell , promoter , microbiology and biotechnology , gene , genetics , gene expression , homeobox
Although the POU transcription factor Oct3/4 is pivotal in maintaining self renewal of embryonic stem (ES) cells, little is known of its molecular mechanisms. We previously reported that the N-terminal transactivation domain of Oct3/4 is required for activation ofLefty1 expression (H. Niwa, S. Masui, I. Chambers, A. G. Smith, and J. Miyazaki, Mol. Cell. Biol.22: 1526-1536, 2002). Here we test whetherLefty1 is a direct target of Oct3/4. We identified an ES cell-specific enhancer upstream of theLefty1 promoter that contains binding sites for Oct3/4 and Sox2. Unlike other known Oct3/4-Sox2-dependent enhancers, however, this enhancer element could not be activated by Oct3/4 and Sox2 in differentiated cells. By functional screening of ES-specific transcription factors, we found that Krüppel-like factor 4 (Klf4) cooperates with Oct3/4 and Sox2 to activateLefty1 expression, and that Klf4 acts as a mediating factor that specifically binds to the proximal element of theLefty1 promoter. DNA microarray analysis revealed that a subset of putative Oct3/4 target genes may be regulated in the same manner. Our findings shed light on a novel function of Oct3/4 in ES cells.