Oct-4
From Wikipedia, the free encyclopedia
POU domain, class 5, transcription factor 1
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Identifiers | |
Symbol | POU5F1 OTF3 |
HUGO | 9221 |
Entrez | 5460 |
OMIM | 164177 |
RefSeq | NM_002701 |
UniProt | Q01860 |
Other data | |
Locus | Chr. 6 p21.31 |
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. 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 [1].
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.[2] In fact gene knockdown of Oct4 promotes differentiation, thereby demonstrating a role for these factors in human embryonic stem cell self-renewal. [3]
With Oct4-deficient and low expression of Oct4, embryos fail to form the inner cell mass, lose pluripotency and differentiate into trophectoderm in mice. Therefore, the level of Oct4 expression in mice is vital for regulating pluripotency and early cell differentiation since one of its main function is to keep embryo from differentiating.
Contents |
[edit] NCBI Information
- OCT4 in 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
- OCT4 in 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
- OCT4 in 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.
- OCT4 in 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.
[edit] Structural Information
conserved domain | POU | homeodomain |
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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. |
[edit] 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. [4]
- 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 downregulation 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 analyses.
[edit] See also
- Enhancer
- Histone
- Nanog (transcription factor)
- Pribnow box
- Promoter
- RNA polymerase
- Sox2
- Transcription factors
- Gene regulatory network
- Bioinformatics
[edit] Sources
- funakoshi PDF
- chemicon "Expression of the POU-domain transcription factor Octamer-4 (Oct-4) is widely regarded as a hallmark of pluripotent stem cells. The relationship of Oct-4 to pluripotent stem cells is indicated by its tightly restricted expression to undifferentiated pluripotent stem cells. Upon differentiation to somatic lineages, the expression of Oct-4 disappears rapidly. Unlike the majority of pluripotent stem cell markers, the biological role of Oct-4 has been well characterized. Studies performed in mice point to the critical role of Oct-4 in the establishment and/or maintenance of pluripotent stem cells in an uncommitted state."
- Young Lab- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells
[edit] Cited references
- ^ 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.
- ^ Looijenga, et al.[1]
- ^ Zaehres H,Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ. [2]
- ^ Hochedlinger, K., Yamada, Y., Beard, C., and Jaenisch, R. (2005). Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121, 465-477. Article
[edit] Oct4 Related Publications
3.G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis
4.Core transcriptional regulatory circuitry in human embryonic stem cells
[edit] External links
CAP - CBF - E2F - KlF - Nanog - NF-kB - Oct-4 - P300/CBP - PIT-1 - Rho/Sigma - R-SMAD - Sox2 - Sp1 - STAT (STAT1, STAT3, STAT5)
Basic-helix-loop-helix: AhR - HIF - MYC - Twist - Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6)
Basic leucine zipper: C/EBP - CREB - AP-1
Basic helix-loop-helix leucine zipper: MITF - SREBP
Nuclear receptors: subfamily 1 (Thyroid hormone, RAR, PPAR, LXR, FXR, Calcitriol, PXR, CAR) - subfamily 2 (HNF4, RXR) - subfamily 3/Steroid hormone (Estrogen, Estrogen related, Glucocorticoid, Mineralocorticoid, Progesterone, Androgen) - subfamily 0 (NR0B1)