Transcriptional regulation of human Oct4 by steroidogenic factor-1

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

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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.

Original languageEnglish
Pages (from-to)1198-1209
Number of pages12
JournalJournal of Cellular Biochemistry
Volume101
Issue number5
DOIs
Publication statusPublished - 2007 Aug 1

Fingerprint

Steroidogenic Factor 1
Binding Sites
Transcription
human NR5A1 protein
Assays
Orphan Nuclear Receptors
Embryonal Carcinoma Stem Cells
Mutagenesis
Tretinoin
Stem cells
Luciferases

Keywords

  • Embryonic carcinoma cells
  • Oct4 promoter
  • SF-1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Yang, H. M., Do, H. J., Kim, D. K., Park, J. K., Chang, W. K., Chung, H. M., ... Kim, J. H. (2007). Transcriptional regulation of human Oct4 by steroidogenic factor-1. Journal of Cellular Biochemistry, 101(5), 1198-1209. https://doi.org/10.1002/jcb.21244

Transcriptional regulation of human Oct4 by steroidogenic factor-1. / Yang, Heung Mo; Do, Hyun Jin; Kim, Dong Ku; Park, Jin Ki; Chang, Won Kyong; Chung, Hyung Min; Choi, Sang-Yun; Kim, Jae Hwan.

In: Journal of Cellular Biochemistry, Vol. 101, No. 5, 01.08.2007, p. 1198-1209.

Research output: Contribution to journalArticle

Yang, HM, Do, HJ, Kim, DK, Park, JK, Chang, WK, Chung, HM, Choi, S-Y & Kim, JH 2007, 'Transcriptional regulation of human Oct4 by steroidogenic factor-1', Journal of Cellular Biochemistry, vol. 101, no. 5, pp. 1198-1209. https://doi.org/10.1002/jcb.21244
Yang HM, Do HJ, Kim DK, Park JK, Chang WK, Chung HM et al. Transcriptional regulation of human Oct4 by steroidogenic factor-1. Journal of Cellular Biochemistry. 2007 Aug 1;101(5):1198-1209. https://doi.org/10.1002/jcb.21244
Yang, Heung Mo ; Do, Hyun Jin ; Kim, Dong Ku ; Park, Jin Ki ; Chang, Won Kyong ; Chung, Hyung Min ; Choi, Sang-Yun ; Kim, Jae Hwan. / Transcriptional regulation of human Oct4 by steroidogenic factor-1. In: Journal of Cellular Biochemistry. 2007 ; Vol. 101, No. 5. pp. 1198-1209.
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