Transcriptional regulation of human Oct4 by steroidogenic factor-1

✍ Scribed by Heung-Mo Yang; Hyun-Jin Do; Dong-Ku Kim; Jin-Ki Park; Won-Kyong Chang; Hyung-Min Chung; Sang-Yun Choi; Jae-Hwan Kim

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 248 KB
• Volume: 101
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21244

✦ Synopsis

Abstract

Oct4 encodes a transcription factor that is involved in the maintenance of self‐renewal in stem cells. Recently, the molecular mechanisms that regulate Oct4 expression have come under investigation. In this study, we demonstrate that the orphan nuclear receptor steroidogenic factor‐1 (SF‐1) behaves as a transcriptional activator of human Oct4 (hOct4) through direct interaction with a SF‐1 binding element in the hOct4 proximal promoter. We found that Oct4 and SF‐1 were co‐expressed in undifferentiated human embryonal carcinoma NCCIT cells and downregulated during retinoic acid‐mediated differentiation. We examined the functional role played by SF‐1 in regulation of hOct4 transcription using a luciferase reporter assay and Western blot analysis. Overexpression of SF‐1 increased up to about threefold hOct4 promoter activity and endogenous hOct4 protein expression. Sequence analysis of the hOct4 promoter revealed that the transcriptional activity was closely linked to Conserved Regions 1 (CR1) and 2 (CR2), which contain three putative SF‐1‐binding sites (1st, 2nd, and 3rd SF‐1). Binding assays and mutagenesis of binding sites indicated that the 1st and 2nd SF‐1 elements (in CR1 and CR2, respectively) might be important cis‐regulatory elements in hOct4 promoter activity. However, differences in response to SF‐1 overexpression between wild‐type and mutant hOct4 promoters revealed that the 1st SF‐1 element is the key binding site for SF‐1‐mediated transcriptional activation. Thus, our data indicate that SF‐1 plays a crucial role in the regulation of hOct4 transcription through direct binding to the 1st SF‐1 in CR1 of the hOct4 proximal promoter. J. Cell. Biochem. 101:1198–1209, 2007. © 2007 Wiley‐Liss, Inc.