Oct-4
1210030
225998249
2008-07-16T11:21:01Z
Boghog2
2428506
added group abbreviation to TF navbox template
{{PBB|geneid=5460}}
'''Oct-4''' is an abbreviation of '''[[Octamer]]-4'''. It is a [[homeobox|homeodomain transcription factor]] of the [[POU family]]. This [[protein]] is critically involved in the self-renewal of undifferentiated embryonic [[stem cell]]s.<ref>[http://jura.wi.mit.edu/young_public/hESregulation/index.html Young Lab- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells] at [[MIT]]</ref> As such, it is frequently used as a [[biomarker (cell)|marker]] for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will actually cause differentiation of the cells <ref>{{cite journal| first=H. |last=Niwa| coauthors=J. Miyazake, A. Smith| year=2000| title=Quantitative expression of Oct3/4 defines differentiation, dedifferentiation, or self-renewal of ES Cells| journal=Nature Genetics| volume=24|pages=372–376 |pmid=10742100| doi=10.1038/74199}}</ref>.
==Expression and function==
Oct-4 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.<ref>{{cite journal |author=Looijenga LH, Stoop H, de Leeuw HP, ''et al'' |title=POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors |journal=Cancer Res. |volume=63 |issue=9 |pages=2244–50 |year=2003 |pmid=12727846}}</ref> In fact gene knockdown of Oct-4 promotes differentiation, thereby demonstrating a role for these factors in human embryonic stem cell self-renewal. <ref>{{cite journal |author=Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ |title=High-efficiency RNA interference in human embryonic stem cells |journal=Stem Cells |volume=23 |issue=3 |pages=299–305 |year=2005 |pmid=15749924 |doi=10.1634/stemcells.2004-0252}}</ref>
Mouse embryos that are Oct-4-deficient or have low expression levels of Oct-4 fail to form the inner cell mass, lose pluripotency and differentiate into trophectoderm. Therefore, the level of Oct-4 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 ==
{| class="wikitable"
| '''Species''' || '''Genetics''' || '''Location'''
|-
| [[Mus musculus]] || GeneID: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=18999 18999], refseq for the protein: [http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_038661.1 NP_038661.1], refseq for mRNA: [http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_013633.1 NM_013633.1] || Genomic Location: NC_000083.4, 35114104..35118822 (Plus Strand). Chromosome: 17,17 B1; 17 19.23 cM
|-
| [[Homo sapiens]]|| GeneID: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=5460 5460], refseq for the protein: [http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_002692.2 NP_002692.2], refseq for mRNA: [http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_002701.3 NM_002701.3]. There are two different isoforms for OCT4 in human, the insoform #2 looks like a N terminal truncation or the #1 [http://www.ncbi.nlm.nih.gov/entrez/sutils/geneprod.fcgi?geneid=5460]. || Genomic Location: NC_000006.10, 31246432-31240107 (Minus Strand). Chromosome: 6, 6p21.31
|-
| [[Rattus norvegicus]] || GeneID: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=294562 294562], refseq for the protein: [http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_001009178.1 NP_001009178], refseq for mRNA: [http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_001009178.1 NM_001009178] || Genomic Location: NW_001084776, 650467-655015 (Minus strand). Chromosome: 20.
|-
| [[Danio rerio]] || GeneID: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=30333 303333], refseq for the protein: [http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_571187.1 NP_571187], reseq for mRNA: [http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_131112.1 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[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=38752]),C.elegans(NCBI-GeneID: 172640[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=172640]) and so on. the two proteis are important in the development of animals.
== Structural Information ==
{| class="wikitable"
|+ '''Conserved Domain'''
! conserved domain !! '''POU'''<ref>{{cite web |url=http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=smart00352&version=v2.09 |title=NCBI CDD smart00352 |accessdate=2007-06-20 |format= |work=}}</ref> !! '''homeodomain'''<ref>{{cite web |url=http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd00086 |title=NCBI CDD cd00086 |accessdate=2007-06-20 |format= |work=}}</ref>
|-
! 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==
Oct-4 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. <ref>{{cite journal |author=Hochedlinger K, Yamada Y, Beard C, Jaenisch R |title=Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues |journal=Cell |volume=121 |issue=3 |pages=465–77 |year=2005 |pmid=15882627 |doi=10.1016/j.cell.2005.02.018}}</ref>
=== Animal model ===
In 2000, Niwa et al used conditional expression and repression in murine embryonic stem (ES) cells to determine requirements for Oct-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 Oct-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 Oct-4 induces loss of pluripotency and dedifferentiation to trophectoderm. Thus, a critical amount of Oct-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 Oct-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 Oct-4 as a one of four essential pluripotent genes (namely, Oct-4, [[SOX2]], c-[[Myc]], and [[Kruppel-like factors|Klf4]]) for [[embryonic stem cell]]s has been well-documented <ref>Yamanaka S, et al. | Generation of germline-competent induced pluripotent stem cells | Nature 2007;448:313-7 | PMID 17554338</ref> <ref>Wernig M, et al. | In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state | Nature 2007;448:318-24 | PMID 17554336</ref> <ref>Maherali N, et al. | Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution | Cell Stem Cell 2007;1:55–70 | [http://dx.doi.org/10.1016/j.stem.2007.05.014 dx.doi.org/10.1016]</ref>, several studies suggested role of these genes in sustaining self-renewal capacity of [[adult stem cell|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|Whitehead Institute in Cambridge]], Massachusetts and his colleagues in Oct 2007 contradicted this hypothesis by documenting no role of Oct-4 in mouse somatic stem cell self-renewal.<ref>Jaenisch et al. | Oct-4 Expression Is Not Required for Mouse Somatic Stem Cell Self-Renewal | Cell Stem Cell 2007;1:403-415 (11-Oct) | [http://dx.doi.org/10.1016/j.stem.2007.07.020 doi=10.1016/j.stem.2007.07.020]</ref> This study now demands further research to identify other factors involved in self-renewal capacity of adult stem cell.
==See also==
*[[Enhancer]]
*[[Histone]]
*[[Nanog (transcription factor)]]
*[[Pribnow box]]
*[[Promoter]]
*[[RNA polymerase]]
*[[Transcription factors]]
*[[Gene regulatory network]]
*[[Bioinformatics]]
*[[Induced Pluripotent Stem Cell|Induced pluripotent stem cells (iPS) Cells]]
==References==
{{Reflist|2}}
==Further reading==
{{refbegin | 2}}
* {{cite journal |author=Lamoury F, Croitoru-Lamoury J, Brew B |title=Undifferentiated mouse mesenchymal stem cells spontaneously express neural and stem cell markers Oct-4 and Rex-1 |journal=Cytotherapy |volume=8 |issue=3 |pages=228–42 |year=2006 |pmid=16793732 |doi=10.1080/14653240600735875}}
* {{cite journal |author=Hough S, Clements I, Welch P, Wiederholt K |title=Differentiation of mouse embryonic stem cells after RNA interference-mediated silencing of OCT4 and Nanog |journal=Stem Cells |volume=24 |issue=6 |pages=1467–75 |year=2006 |pmid=16456133 |doi=10.1634/stemcells.2005-0475}}
* {{cite journal |author=Feldman N, Gerson A, Fang J et al |title=G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis |journal=Nat. Cell Biol. |volume=8 |issue=2 |pages=188–94 |year=2006 |pmid=16415856 |doi=10.1038/ncb1353}}
* {{cite journal |author=Boyer L, Lee T, Cole M et al|title=Core transcriptional regulatory circuitry in human embryonic stem cells |journal=Cell |volume=122 |issue=6 |pages=947–56 |year=2005 |pmid=16153702 |doi=10.1016/j.cell.2005.08.020}}
* {{cite journal |author=Gerrard L, Zhao D, Clark A, Cui W |title=Stably transfected human embryonic stem cell clones express OCT4-specific green fluorescent protein and maintain self-renewal and pluripotency |journal=Stem Cells |volume=23 |issue=1 |pages=124–33 |year=2005 |pmid=15625129 |doi=10.1634/stemcells.2004-0102}}
* {{cite journal |author=Reményi A, Lins K, Nissen L et al |title=Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers |journal=Genes Dev. |volume=17 |issue=16 |pages=2048–59 |year=2003 |pmid=12923055 |doi=10.1101/gad.269303}}
{{PBB_Further_reading
| citations =
*{{cite journal | author=Takeda J, Seino S, Bell GI |title=Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues |journal=Nucleic Acids Res. |volume=20 |issue= 17 |pages= 4613–20 |year= 1992 |pmid= 1408763 |doi= 10.1093/nar/20.17.4613}}
*{{cite journal | author=Schoorlemmer J, Kruijer W |title=Octamer-dependent regulation of the kFGF gene in embryonal carcinoma and embryonic stem cells |journal=Mech. Dev. |volume=36 |issue= 1-2 |pages= 75–86 |year= 1992 |pmid= 1723621 |doi=10.1016/0925-4773(91)90074-G }}
*{{cite journal | author=Wey E, Lyons GE, Schäfer BW |title=A human POU domain gene, mPOU, is expressed in developing brain and specific adult tissues |journal=Eur. J. Biochem. |volume=220 |issue= 3 |pages= 753–62 |year= 1994 |pmid= 7908264 |doi= 10.1111/j.1432-1033.1994.tb18676.x}}
*{{cite journal | author=Crouau-Roy B, Amadou C, Bouissou C, ''et al.'' |title=Localization of the OTF3 gene within the human MHC class I region by physical and meiotic mapping |journal=Genomics |volume=21 |issue= 1 |pages= 241–3 |year= 1994 |pmid= 8088794 |doi= 10.1006/geno.1994.1249 }}
*{{cite journal | author=Guillaudeux T, Mattei MG, Depetris D, ''et al.'' |title=In situ hybridization localizes the human OTF3 to chromosome 6p21.3-->p22 and OTF3L to 12p13 |journal=Cytogenet. Cell Genet. |volume=63 |issue= 4 |pages= 212–4 |year= 1993 |pmid= 8500351 |doi=10.1159/000133537 }}
*{{cite journal | author=Abdel-Rahman B, Fiddler M, Rappolee D, Pergament E |title=Expression of transcription regulating genes in human preimplantation embryos |journal=Hum. Reprod. |volume=10 |issue= 10 |pages= 2787–92 |year= 1996 |pmid= 8567814 |doi= }}
*{{cite journal | author=Hillier LD, Lennon G, Becker M, ''et al.'' |title=Generation and analysis of 280,000 human expressed sequence tags |journal=Genome Res. |volume=6 |issue= 9 |pages= 807–28 |year= 1997 |pmid= 8889549 |doi=10.1101/gr.6.9.807 }}
*{{cite journal | author=Inamoto S, Segil N, Pan ZQ, ''et al.'' |title=The cyclin-dependent kinase-activating kinase (CAK) assembly factor, MAT1, targets and enhances CAK activity on the POU domains of octamer transcription factors |journal=J. Biol. Chem. |volume=272 |issue= 47 |pages= 29852–8 |year= 1997 |pmid= 9368058 |doi= 10.1074/jbc.272.47.29852}}
*{{cite journal | author=Nichols J, Zevnik B, Anastassiadis K, ''et al.'' |title=Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4 |journal=Cell |volume=95 |issue= 3 |pages= 379–91 |year= 1998 |pmid= 9814708 |doi= 10.1016/S0092-8674(00)81769-9}}
*{{cite journal | author=Gonzalez MI, Robins DM |title=Oct-1 preferentially interacts with androgen receptor in a DNA-dependent manner that facilitates recruitment of SRC-1 |journal=J. Biol. Chem. |volume=276 |issue= 9 |pages= 6420–8 |year= 2001 |pmid= 11096094 |doi= 10.1074/jbc. M008689200 }}
*{{cite journal | author=Butteroni C, De Felici M, Schöler HR, Pesce M |title=Phage display screening reveals an association between germline-specific transcription factor Oct-4 and multiple cellular proteins |journal=J. Mol. Biol. |volume=304 |issue= 4 |pages= 529–40 |year= 2001 |pmid= 11099378 |doi= 10.1006/jmbi.2000.4238 }}
*{{cite journal | author=Ezashi T, Ghosh D, Roberts RM |title=Repression of Ets-2-induced transactivation of the tau interferon promoter by Oct-4 |journal=Mol. Cell. Biol. |volume=21 |issue= 23 |pages= 7883–91 |year= 2001 |pmid= 11689681 |doi= 10.1128/MCB.21.23.7883-7891.2001 }}
*{{cite journal | author=Guo Y, Costa R, Ramsey H, ''et al.'' |title=The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 6 |pages= 3663–7 |year= 2002 |pmid= 11891324 |doi= 10.1073/pnas.062041099 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal | author=Looijenga LH, Stoop H, de Leeuw HP, ''et al.'' |title=POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors |journal=Cancer Res. |volume=63 |issue= 9 |pages= 2244–50 |year= 2003 |pmid= 12727846 |doi= }}
*{{cite journal | author=Wang P, Branch DR, Bali M, ''et al.'' |title=The POU homeodomain protein OCT3 as a potential transcriptional activator for fibroblast growth factor-4 (FGF-4) in human breast cancer cells |journal=Biochem. J. |volume=375 |issue= Pt 1 |pages= 199–205 |year= 2003 |pmid= 12841847 |doi= 10.1042/BJ20030579 }}
*{{cite journal | author=Reményi A, Lins K, Nissen LJ, ''et al.'' |title=Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers |journal=Genes Dev. |volume=17 |issue= 16 |pages= 2048–59 |year= 2003 |pmid= 12923055 |doi= 10.1101/gad.269303 }}
*{{cite journal | author=Rajpert-De Meyts E, Hanstein R, Jørgensen N, ''et al.'' |title=Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads |journal=Hum. Reprod. |volume=19 |issue= 6 |pages= 1338–44 |year= 2004 |pmid= 15105401 |doi= 10.1093/humrep/deh265 }}
*{{cite journal | author=Matin MM, Walsh JR, Gokhale PJ, ''et al.'' |title=Specific knockdown of Oct4 and beta2-microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells |journal=Stem Cells |volume=22 |issue= 5 |pages= 659–68 |year= 2005 |pmid= 15342930 |doi= 10.1634/stemcells.22-5-659 }}
*{{cite journal | author=Baal N, Reisinger K, Jahr H, ''et al.'' |title=Expression of transcription factor Oct-4 and other embryonic genes in CD133 positive cells from human umbilical cord blood |journal=Thromb. Haemost. |volume=92 |issue= 4 |pages= 767–75 |year= 2005 |pmid= 15467907 |doi= 10.1267/THRO04040767 |doi_brokendate=2008-06-22 }}
}}
{{refend}}
==External links==
* {{MeshName|Oct-4+Transcription+Factor}}
* [http://www.jove.com/index/details.stp?ID=734 Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4]
{{Transcription factors|g3}}
[[Category:Transcription factors]]
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