PMID- 16954384 OWN - NLM STAT- MEDLINE DCOM- 20061113 LR - 20211203 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 26 IP - 20 DP - 2006 Oct TI - Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. PG - 7772-82 AB - 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 of Lefty1 expression (H. Niwa, S. Masui, I. Chambers, A. G. Smith, and J. Miyazaki, Mol. Cell. Biol. 22:1526-1536, 2002). Here we test whether Lefty1 is a direct target of Oct3/4. We identified an ES cell-specific enhancer upstream of the Lefty1 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 Kruppel-like factor 4 (Klf4) cooperates with Oct3/4 and Sox2 to activate Lefty1 expression, and that Klf4 acts as a mediating factor that specifically binds to the proximal element of the Lefty1 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. FAU - Nakatake, Yuhki AU - Nakatake Y AD - Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Minatojima-Minamimachi 2-2-3, Chu-o-ku, Kobe 650-0047, Japan. FAU - Fukui, Nobutaka AU - Fukui N FAU - Iwamatsu, Yuko AU - Iwamatsu Y FAU - Masui, Shinji AU - Masui S FAU - Takahashi, Kadue AU - Takahashi K FAU - Yagi, Rika AU - Yagi R FAU - Yagi, Kiyohito AU - Yagi K FAU - Miyazaki, Jun-Ichi AU - Miyazaki J FAU - Matoba, Ryo AU - Matoba R FAU - Ko, Minoru S H AU - Ko MS FAU - Niwa, Hitoshi AU - Niwa H LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20060905 PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (HMGB Proteins) RN - 0 (KLF4 protein, human) RN - 0 (Klf4 protein, mouse) RN - 0 (Kruppel-Like Factor 4) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (Left-Right Determination Factors) RN - 0 (Lefty1 protein, mouse) RN - 0 (Membrane Proteins) RN - 0 (Organic Cation Transport Proteins) RN - 0 (Sex-Determining Region Y Protein) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Animals MH - Base Sequence MH - Binding Sites MH - Cell Differentiation MH - Conserved Sequence MH - Embryo, Mammalian/cytology/metabolism MH - Gene Expression/genetics MH - Genes, Reporter/genetics MH - HMGB Proteins/genetics/*metabolism MH - Humans MH - Kruppel-Like Factor 4 MH - Kruppel-Like Transcription Factors/genetics/*metabolism MH - Left-Right Determination Factors MH - Membrane Proteins/*genetics/metabolism MH - Mice MH - Organic Cation Transport Proteins/genetics/*metabolism MH - Promoter Regions, Genetic/*genetics MH - Protein Binding MH - Sex-Determining Region Y Protein/genetics/*metabolism MH - Stem Cells/cytology/*metabolism MH - Transforming Growth Factor beta/*genetics/metabolism PMC - PMC1636862 EDAT- 2006/09/07 09:00 MHDA- 2006/11/14 09:00 PMCR- 2007/02/01 CRDT- 2006/09/07 09:00 PHST- 2006/09/07 09:00 [pubmed] PHST- 2006/11/14 09:00 [medline] PHST- 2006/09/07 09:00 [entrez] PHST- 2007/02/01 00:00 [pmc-release] AID - MCB.00468-06 [pii] AID - 0468-06 [pii] AID - 10.1128/MCB.00468-06 [doi] PST - ppublish SO - Mol Cell Biol. 2006 Oct;26(20):7772-82. doi: 10.1128/MCB.00468-06. Epub 2006 Sep 5.