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Gene POU5F1: Gene PO5F1_HUMAN
POU domain, class 5, transcription factor 1
NCBI/Entrez 5460
HGNC 9221
UniProt/Swiss-Prot/ UniProt/TrEMBL Q01860, Q5STF3, Q5STD5,
Ensembl ENSG00000204531
OMIM 164177
GeneCards GC06M031240
Synonyms: MGC22487, OCT3, Oct-3, Oct4, OCT4, Oct-4, Octamer-binding transcription factor 3, OTF3, OTF4

OCT4 (Gene Pou5F1)

Pou genes code a family of transcription factors that contain a Pit1-Oct-Unc86 (POU) region composed of two domains, POU-specific and POU-homeo, which together form a bipartite bond with DNA. The POU5F1 gene (map locus 6p21.31) product, OCT4, is an octamer (5'-ATTTGCAT-3') motif-binding transcription factor that forms a trimeric complex with DNA and SOX2. Two isoforms of OCT4 result from alternative splicing, OCT3A (OCT4) and OCT3B (OCT4B). Isoform OCT3A is 360 amino acids long (38.6 kDa) while isoform B is truncated to 265 amino acids. The C-terminal 225 amino acids of each isoform are identical. Post-translational modification by sumoylation stabilizes OCT4 and enhances its DNA binding and transactivation activity.

Oct4 is a marker for germ-line (oocytes), undifferentiated (pluripotent) and tumor cells. Its principle function is to block differentiation, while allowing proliferation. OCT4 has emerged as a master regulator of cell pluripotency and lineage commitment. Whether a cell maintains pluripotency or differentiates is dependent upon the precise levels of OCT4 expression. Levels above normal induce differentiation towards primitive endoderm and mesoderm; whereas, subnormal levels lead to loss of pluripotency and dedifferentiation to trophectoderm, Niwa H, et al. (2000). OCT4 controls early embryogenesis and stem cell pluripotency thru regulation of genes such as YES1, FGF4, UTF1 and ZFP206. OCT4 frequently partners with Nanog in repressor complexes that control embryonic stem cell fate.

The importance of OCT4 has been elevated by the findings that it along with SOX-2, c-Myc and Klf4 can induced dedifferentiation of fibroblasts (differentiated) to induced pluripotent stem cells (iPS), Takahashi and Yamanaka, 2006. OCT4 positive cells selected for Nanog expression result in germ-line competent iPS cells with gene expression and methylation patterns very similar to embryonic stem (ES) cells, Okita et al. (2007). Wernig et al. (2007) showed that cells with reactivated endogenous OCT4 (OCT4-neo) or Nanog (Nanog-neo) were epigenetically identical to ES cells. Using Oct4, Sox2, Klf4, and Myc, Park et al. (2008) derived induced pluripotent stem (iPS) cells from fetal, neonatal, and adult human primary cells, including dermal fibroblasts. Yu et al. (2007) showed that 4 factors, OCT4, SOX2, NANOG, and LIN28, are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem cells.

OCT4 activity is inhibited by PIAS proteins (PIAS1, PIAS2, PIASy) that sequester OCT4 to the nuclear periphery, Tolkunova E, (2007).

Sigma offers antibodies, shRNAs and other products useful for the study of the POU5F1 Gene.



References:

Niwa H, Miyazaki J, Smith AG. (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet. 24: 372-376.

Okita, K.; Ichisaka, T.; Yamanaka, S. (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448: 313-317.

Park, I.-H.; Zhao, R.; West, J. A.; Yabuuchi, A.; Huo, H.; Ince, T. A.; Lerou, P. H.; Lensch, M. W.; Daley, G. Q. (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451: 141-146.

Takahashi, K.; Yamanaka, S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663-676.

Tolkunova E, Malashicheva A, Parfenov VN, Sustmann C, Grosschedl R, Tomilin A. (2007) PIAS proteins as repressors of Oct4 function. J Mol Biol. 374: 1200-1212.

Yu, J.; Vodyanik, M. A.; Smuga-Otto, K.; Antosiewicz-Bourget, J.; Frane, J. L.; Tian, S.; Nie, J.; Jonsdottir, G. A.; Ruotti, V.; Stewart, R.; Slukvin, I. I.; Thomson, J. A. (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318: 1917-1920.

Wernig, M.; Meissner, A.; Foreman, R.; Brambrink, T.; Ku, M.; Hochedlinger, K.; Bernstein, B. E.; Jaenisch, R. (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448: 318-324.

Wei F, Scholer HR, Atchison ML. (2007) Sumoylation of Oct4 enhances its stability, DNA binding, and transactivation. J Biol Chem. 282: 21551-21560.

Footnote: Gene Data Sources: HGNC, Entrez Gene, UniProt/Swiss-Prot, UniProt/TrEMBL, GDB, OMIM, GeneLoc, Ensembl.

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