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Oct-4




POU domain, class 5, transcription factor 1
Identifiers
Symbol(s) POU5F1; MGC22487; OCT3; OCT4; OTF3; OTF4
External IDs OMIM: 164177 MGI: 101893 Homologene: 8422
RNA expression pattern

More reference expression data

Orthologs
Human Mouse
Entrez 5460 18999
Ensembl ENSG00000204531 ENSMUSG00000024406
Uniprot Q01860 na
Refseq NM_002701 (mRNA)
NP_002692 (protein) 		NM_013633 (mRNA)
NP_038661 (protein)
Location Chr 6: 31.24 - 31.25 Mb Chr 17: 35.11 - 35.12 Mb
Pubmed search [1] [2]

Oct-4 is an abbreviation of Octamer-4. It is a homeodomain transcription factor of the POU family. This protein is critically involved in the self-renewal of undifferentiated embryonic stem cells.[1] As such, it is frequently used as a marker for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will actually cause differentiation of the cells [2].

Contents

Expression and function

Oct4 is expressed in developing embryos throughout the preimplantation period. This transcription factor is initially active as a maternal factor in the oocyte but remains active in embryos throughout the preimplantation period. Oct-4 expression is associated with an undifferentiated phenotype and tumors.[3] In fact gene knockdown of Oct4 promotes differentiation, thereby demonstrating a role for these factors in human embryonic stem cell self-renewal. [4]

Mouse embryos that are Oct4-deficient or have low expression levels of Oct4 fail to form the inner cell mass, lose pluripotency and differentiate into trophectoderm. Therefore, the level of Oct4 expression in mice is vital for regulating pluripotency and early cell differentiation since one of its main functions is to keep the embryo from differentiating.

NCBI Information

Species Genetics Location
Mus musculus GeneID: 18999, refseq for the protein: NP_038661.1, refseq for mRNA: NM_013633.1 Genomic Location: NC_000083.4, 35114104..35118822 (Plus Strand). Chromosome: 17,17 B1; 17 19.23 cM
Homo sapiens GeneID: 5460, refseq for the protein: NP_002692.2, refseq for mRNA: NM_002701.3. There are two different isoforms for OCT4 in human, the insoform #2 looks like a N terminal truncation or the #1 [3]. Genomic Location: NC_000006.10, 31246432-31240107 (Minus Strand). Chromosome: 6, 6p21.31
Rattus norvegicus GeneID: 294562, refseq for the protein: NP_001009178, refseq for mRNA: NM_001009178 Genomic Location: NW_001084776, 650467-655015 (Minus strand). Chromosome: 20.
Danio rerio GeneID: 303333, refseq for the protein: NP_571187, reseq for mRNA: NM_131112 Genomic Location: NC_007127.1, 27995548-28000317 (Minus strand). Chromosome: 21.

Different alignment methods will give the different results about the orthologs. there are other orthologs from Drosophila(NCBI-GeneID: 38752[4]),C.elegans(NCBI-GeneID: 172640[5]) and so on. the two proteis are important in the development of animals.

Structural Information

Conserved Domain
conserved domain POU[5] homeodomain[6]
Length 75aa 59aa
Description Found in Pit-Oct-Unc transcription factors DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

Implications in Disease

Oct4 has been implicated in tumorigenesis of adult germ cells. Ectopic expression of the factor in adult mice has been found to cause the formation of dysplastic lesions of the skin and intestine. The intestinal dysplasia resulted from an increase in progenitor cell population and the upregulation of β-catenin transcription through the inhibition of cellular differentiation. [7]

Animal model

In 2000, Niwa et al used conditional expression and repression in murine embryonic stem (ES) cells to determine requirements for Oct3/4 in the maintenance of developmental potency. Although transcriptional determination has usually been considered as a binary on-off control system, they found that the precise level of Oct3/4 governs 3 distinct fates of ES cells. A less-than-2-fold increase in expression causes differentiation into primitive endoderm and mesoderm. In contrast, repression of Oct3/4 induces loss of pluripotency and dedifferentiation to trophectoderm. Thus, a critical amount of Oct3/4 is required to sustain stVentral veinlessem cell self-renewal, and up- or down regulation induces divergent developmental programs. Niwa et al suggested that their findings established a role for Oct3/4 as a master regulator of pluripotency that controls lineage commitment and illustrated the sophistication of critical transcriptional regulators and the consequent importance of quantitative analyzes.

Although role of Oct4 as a one of four essential pluripotent genes (namely, Oct3/4, Sox2, c-Myc, and Klf4) for embryonic stem cells has been well-documented [8] [9] [10], several studies suggested role of these genes in sustaining self-renewal capacity of adult somatic stem cells (i.e. Stem cells from intestinal epithelium, bone marrow, retina, brain, liver, etc.). These genes are thought to be active in such adult stem cells in low quantity. However, Jaenisch at the Whitehead Institute in Cambridge, Massachusetts and his colleagues in Oct 2007 contradicted this hypothesis by documenting no role of Oct4 in mouse somatic stem cell self-renewal.[11] This study now demands further research to identify other factors involved in self-renewal capacity of adult stem cell.

See also

References

  1. ^ Young Lab- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells at MIT
  2. ^ Niwa, H.; J. Miyazake, A. Smith (2000). "Quantitative expression of Oct3/4 defines differentiation, dedifferentiation, or self-renewal of ES Cells". Nature Genetics 24: 372-376. PMID 10742100.
  3. ^ Looijenga LH, Stoop H, de Leeuw HP, et al (2003). "POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors". Cancer Res. 63 (9): 2244-50. PMID 12727846.
  4. ^ Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ (2005). "High-efficiency RNA interference in human embryonic stem cells". Stem Cells 23 (3): 299-305. doi:10.1634/stemcells.2004-0252. PMID 15749924.
  5. ^ NCBI CDD smart00352. Retrieved on 2007-06-20.
  6. ^ NCBI CDD cd00086. Retrieved on 2007-06-20.
  7. ^ Hochedlinger K, Yamada Y, Beard C, Jaenisch R (2005). "Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues". Cell 121 (3): 465-77. doi:10.1016/j.cell.2005.02.018. PMID 15882627.
  8. ^ Yamanaka S, et. al. | Generation of germline-competent induced pluripotent stem cells | Nature 2007;448:313-7 | PMID 17554338
  9. ^ Wernig M, et. al. | In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state | Nature 2007;448:318-24 | PMID 17554336
  10. ^ Maherali N, et. al. | Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution | Cell Stem Cell 2007;1:55–70 | dx.doi.org/10.1016
  11. ^ Jaenisch et al. | Oct4 Expression Is Not Required for Mouse Somatic Stem Cell Self-Renewal | Cell Stem Cell 2007;1:403-415 (11-Oct) | doi:10.1016/j.stem.2007.07.020

Further reading

  • Lamoury F, Croitoru-Lamoury J, Brew B (2006). "Undifferentiated mouse mesenchymal stem cells spontaneously express neural and stem cell markers Oct-4 and Rex-1". Cytotherapy 8 (3): 228-42. PMID 16793732.
  • Hough S, Clements I, Welch P, Wiederholt K (2006). "Differentiation of mouse embryonic stem cells after RNA interference-mediated silencing of OCT4 and Nanog". Stem Cells 24 (6): 1467-75. PMID 16456133.
  • Feldman N, Gerson A, Fang J et al (2006). "G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis". Nat. Cell Biol. 8 (2): 188-94. PMID 16415856.
  • Boyer L, Lee T, Cole M et al (2005). "Core transcriptional regulatory circuitry in human embryonic stem cells". Cell 122 (6): 947-56. PMID 16153702.
  • Gerrard L, Zhao D, Clark A, Cui W (2005). "Stably transfected human embryonic stem cell clones express OCT4-specific green fluorescent protein and maintain self-renewal and pluripotency". Stem Cells 23 (1): 124-33. PMID 15625129.
  • Reményi A, Lins K, Nissen L et al (2003). "Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers". Genes Dev. 17 (16): 2048-59. PMID 12923055.
  • Takeda J, Seino S, Bell GI (1992). "Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues.". Nucleic Acids Res. 20 (17): 4613-20. PMID 1408763.
  • Schoorlemmer J, Kruijer W (1992). "Octamer-dependent regulation of the kFGF gene in embryonal carcinoma and embryonic stem cells.". Mech. Dev. 36 (1-2): 75-86. PMID 1723621.
  • Wey E, Lyons GE, Schäfer BW (1994). "A human POU domain gene, mPOU, is expressed in developing brain and specific adult tissues.". Eur. J. Biochem. 220 (3): 753-62. PMID 7908264.
  • Crouau-Roy B, Amadou C, Bouissou C, et al. (1994). "Localization of the OTF3 gene within the human MHC class I region by physical and meiotic mapping.". Genomics 21 (1): 241-3. doi:10.1006/geno.1994.1249. PMID 8088794.
  • Guillaudeux T, Mattei MG, Depetris D, et al. (1993). "In situ hybridization localizes the human OTF3 to chromosome 6p21.3-->p22 and OTF3L to 12p13.". Cytogenet. Cell Genet. 63 (4): 212-4. PMID 8500351.
  • Abdel-Rahman B, Fiddler M, Rappolee D, Pergament E (1996). "Expression of transcription regulating genes in human preimplantation embryos.". Hum. Reprod. 10 (10): 2787-92. PMID 8567814.
  • Hillier LD, Lennon G, Becker M, et al. (1997). "Generation and analysis of 280,000 human expressed sequence tags.". Genome Res. 6 (9): 807-28. PMID 8889549.
  • Inamoto S, Segil N, Pan ZQ, et al. (1997). "The cyclin-dependent kinase-activating kinase (CAK) assembly factor, MAT1, targets and enhances CAK activity on the POU domains of octamer transcription factors.". J. Biol. Chem. 272 (47): 29852-8. PMID 9368058.
  • Nichols J, Zevnik B, Anastassiadis K, et al. (1998). "Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.". Cell 95 (3): 379-91. PMID 9814708.
  • Gonzalez MI, Robins DM (2001). "Oct-1 preferentially interacts with androgen receptor in a DNA-dependent manner that facilitates recruitment of SRC-1.". J. Biol. Chem. 276 (9): 6420-8. doi:10.1074/jbc.M008689200. PMID 11096094.
  • Butteroni C, De Felici M, Schöler HR, Pesce M (2001). "Phage display screening reveals an association between germline-specific transcription factor Oct-4 and multiple cellular proteins.". J. Mol. Biol. 304 (4): 529-40. doi:10.1006/jmbi.2000.4238. PMID 11099378.
  • Ezashi T, Ghosh D, Roberts RM (2001). "Repression of Ets-2-induced transactivation of the tau interferon promoter by Oct-4.". Mol. Cell. Biol. 21 (23): 7883-91. doi:10.1128/MCB.21.23.7883-7891.2001. PMID 11689681.
  • Guo Y, Costa R, Ramsey H, et al. (2002). "The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression.". Proc. Natl. Acad. Sci. U.S.A. 99 (6): 3663-7. doi:10.1073/pnas.062041099. PMID 11891324.
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899-903. doi:10.1073/pnas.242603899. PMID 12477932.
  • Looijenga LH, Stoop H, de Leeuw HP, et al. (2003). "POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors.". Cancer Res. 63 (9): 2244-50. PMID 12727846.
  • Wang P, Branch DR, Bali M, et al. (2003). "The POU homeodomain protein OCT3 as a potential transcriptional activator for fibroblast growth factor-4 (FGF-4) in human breast cancer cells.". Biochem. J. 375 (Pt 1): 199-205. doi:10.1042/BJ20030579. PMID 12841847.
  • Reményi A, Lins K, Nissen LJ, et al. (2003). "Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers.". Genes Dev. 17 (16): 2048-59. doi:10.1101/gad.269303. PMID 12923055.
  • Rajpert-De Meyts E, Hanstein R, Jørgensen N, et al. (2004). "Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads.". Hum. Reprod. 19 (6): 1338-44. doi:10.1093/humrep/deh265. PMID 15105401.
  • Matin MM, Walsh JR, Gokhale PJ, et al. (2005). "Specific knockdown of Oct4 and beta2-microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells.". Stem Cells 22 (5): 659-68. doi:10.1634/stemcells.22-5-659. PMID 15342930.
  • Baal N, Reisinger K, Jahr H, et al. (2005). "Expression of transcription factor Oct-4 and other embryonic genes in CD133 positive cells from human umbilical cord blood.". Thromb. Haemost. 92 (4): 767-75. doi:10.1267/THRO04040767. PMID 15467907.
v • d • e
Transcription factors and intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP) Activating transcription factor (1, 2, 3, 4, 5, 6) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3) • GABPA • MAF (B, F, G, K) • NRL • NRF1 • XBP1
(1.2) Basic helix-loop-helix (bHLH) ATOH1 • AhR • AHRR • ARNT • ASCL1 • BMAL (ARNTL, ARNTL2) • CLOCK • HIF (1A, 3A) • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • NEUROD1 • Twist • USF1
(1.3) bHLH-ZIP Myc • MITF • SREBP (1, 2)
(1.6) Basic helix-span-helix (bHSH) AP-2
(2) Zinc finger
DNA-binding domains
(2.1) Nuclear receptor (Cys4) subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) • subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) • subfamily 3 (Steroid hormone (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • subfamily 4 NUR (NGFIB, NOR1, NURR1) • subfamily 5 (LRH-1, SF1) • subfamily 6 (GCNF) • subfamily 0 (DAX1, SHP)
(2.2) Other Cys4 GATA (1, 2, 3, 4, 5, 6)
(2.3) Cys2His2 General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH: 1, 2) • GLI-Krüppel family (1, 2, 3, YY1) • KLF (2, 4, 5, 6, 10, 11, 12, 13) • Sp1 • zinc finger (3, 35, 43, 146, 148, 165, 217, 268, 281, 350) • Zbtb7 (7A) • ZBT (16, 17, 33)
(2.4) Cys6 HIVEP1
(3) Helix-turn-helix
domains
(3.1) Homeo domain ARX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C6, C8, C9, C13, D1, D3, D4, D9, D10, D11, D12, D13) • NANOG • NKX (2-1, 2-5, 3-1) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7)
(3.2) Paired box PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)
(3.3) Fork head / winged helix E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, L2, M1, N3, O3, O4, P1, P2, P3)
(3.4) Heat Shock Factors HSF1
(3.5) Tryptophan clusters ELF (4, 5) • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB
(3.6) TEA domain transcriptional enhancer factor 1, 2
(4) β-Scaffold factors with
minor groove contacts
(4.1) Rel homology region NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (5, C1, C2, C3, C4)
(4.2) STAT STAT (1, 2, 3, 4, 5, 6)
(4.3) p53 p53
(4.4) MADS box Mef2 (A, B, C, D) • SRF
(4.7) High mobility group HNF (1A, 1B) • LEF1 • SOX (3, 4, 6, 9, 10, 13, 18) • SRY • SSRP1
(4.10) Cold-shock domain CSDA
(4.11) Runt CBF (RUNX1, RUNX2, RUNX3)
(0) Other
transcription factors
(0.2) HMGI(Y) HMGA (1, 2)
(0.3) Pocket domain Rb • RBL1 • RBL2
(0.6) Miscellaneous ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • Rho/Sigma • R-SMAD
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Oct-4". A list of authors is available in Wikipedia.
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