Oct-4

Oct-4 transcription factor is initially active as a maternal factor in the oocyte and remains active in embryos throughout the preimplantation period. Oct-4 expression is associated with an undifferentiated phenotype and tumors.{{cite journal | vauthors = Looijenga LH, Stoop H, de Leeuw HP, de Gouveia Brazao CA, Gillis AJ, van Roozendaal KE, van Zoelen EJ, Weber RF, Wolffenbuttel KP, van Dekken H, Honecker F, Bokemeyer C, Perlman EJ, Schneider DT, Kononen J, Sauter G, Oosterhuis JW | title = POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors | journal = Cancer Research | volume = 63 | issue = 9 | pages = 2244–50 | date = May 2003 | pmid = 12727846 }} Gene knockdown of Oct-4 promotes differentiation, demonstrating a role for these factors in human embryonic stem cell self-renewal.{{cite journal | vauthors = 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 | date = March 2005 | pmid = 15749924 | doi = 10.1634/stemcells.2004-0252 | s2cid = 1395518 | doi-access = free }} Oct-4 can form a heterodimer with Sox2, so that these two proteins bind DNA together.{{cite journal | vauthors = Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, Robson P | title = Transcriptional regulation of nanog by OCT4 and SOX2 | journal = The Journal of Biological Chemistry | volume = 280 | issue = 26 | pages = 24731–7 | date = July 2005 | pmid = 15860457 | doi = 10.1074/jbc.M502573200 | doi-access = free }}

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.

Orthologs of Oct-4 in humans and other species include:

Oct-4 contains the following protein domains:

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.{{cite journal | vauthors = 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 | date = May 2005 | pmid = 15882627 | doi = 10.1016/j.cell.2005.02.018 | s2cid = 1913872 | doi-access = free }}

In 2000, Niwa et al. used conditional expression and repression in murine embryonic stem cells to determine requirements for Oct-4 in the maintenance of developmental potency. Although transcriptional determination has often 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. An increase in expression of less than 2-fold 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 stem cell self-renewal, and up- or down-regulation induces divergent developmental programs. Changes to Oct-4 levels do not independently promote differentiation, but are also controlled by levels of Sox2. A decrease in Sox2 accompanies increased levels of Oct-4 to promote a mesendodermal fate, with Oct-4 actively inhibiting ectodermal differentiation. Repressed Oct-4 levels that lead to ectodermal differentiation are accompanied by an increase in Sox2, which effectively inhibits mesendodermal differentiation.{{cite journal | vauthors = Thomson M, Liu SJ, Zou LN, Smith Z, Meissner A, Ramanathan S | title = Pluripotency factors in embryonic stem cells regulate differentiation into germ layers | journal = Cell | volume = 145 | issue = 6 | pages = 875–89 | date = June 2011 | pmid = 21663792 | pmc = 5603300 | doi = 10.1016/j.cell.2011.05.017 }} 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.

The transcription factors Oct-4, Sox2, and Nanog are part of a complex regulatory network, with Oct-4 and Sox2 being capable of directly regulating Nanog by binding to its promoter, and are essential for maintaining the self-renewing undifferentiated state of the inner cell mass of the blastocyst, embryonic stem cell linesHeurtier, V., Owens, N., Gonzalez, I. et al. The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells. Nat Commun 10, 1109 (2019). https://doi.org/10.1038/s41467-019-09041-z (which are cell lines derived from the inner cell mass), and induced pluripotent stem cells. While differential up- and down-regulation of Oct-4 and Sox2 has been shown to promote differentiation, down-regulation of Nanog must occur for differentiation to proceed.

Oct-4 is one of the transcription factors that is used to create induced pluripotent stem cells (iPSCs), together with Sox2, Klf4, and often c-Myc (OSKM) in mice,{{cite journal | vauthors = Okita K, Ichisaka T, Yamanaka S | title = Generation of germline-competent induced pluripotent stem cells | journal = Nature | volume = 448 | issue = 7151 | pages = 313–7 | date = July 2007 | pmid = 17554338 | doi = 10.1038/nature05934 | bibcode = 2007Natur.448..313O | s2cid = 459050 }}{{cite journal | vauthors = Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R | title = In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state | journal = Nature | volume = 448 | issue = 7151 | pages = 318–24 | date = July 2007 | pmid = 17554336 | doi = 10.1038/nature05944 | bibcode = 2007Natur.448..318W | s2cid = 4377572 }}{{cite journal | vauthors = Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, Plath K, Hochedlinger K | title = Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution | journal = Cell Stem Cell | volume = 1 | issue = 1 | pages = 55–70 | date = June 2007 | pmid = 18371336 | doi = 10.1016/j.stem.2007.05.014 | doi-access = free }} demonstrating its capacity to induce an embryonic stem-cell-like state. These factors are often referred to as "Yamanaka reprogramming factors". This reprogramming effect has also been seen with the Thomson reprogramming factors, reverting human fibroblast cells to iPSCs via Oct-4, along with Sox2, Nanog, and Lin28. The use of Thomson reprogramming factors avoids the need to overexpress c-Myc, an oncogene.{{cite journal | vauthors = Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA | title = Induced pluripotent stem cell lines derived from human somatic cells | journal = Science | volume = 318 | issue = 5858 | pages = 1917–20 | date = December 2007 | pmid = 18029452 | doi = 10.1126/science.1151526 | bibcode = 2007Sci...318.1917Y | s2cid = 86129154 }} It was later determined that only two of these four factors, namely Oct4 and Klf4, are sufficient to reprogram mouse adult neural stem cells.{{cite journal | vauthors = Kim JB, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, Araúzo-Bravo MJ, Ruau D, Han DW, Zenke M, Schöler HR | title = Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors | journal = Nature | volume = 454 | issue = 7204 | pages = 646–50 | date = July 2008 | pmid = 18594515 | doi = 10.1038/nature07061 | bibcode = 2008Natur.454..646K | s2cid = 4318637 }} Finally it was shown that a single factor, Oct-4 was sufficient for this transformation.{{cite journal | vauthors = Kim JB, Sebastiano V, Wu G, Araúzo-Bravo MJ, Sasse P, Gentile L, Ko K, Ruau D, Ehrich M, van den Boom D, Meyer J, Hübner K, Bernemann C, Ortmeier C, Zenke M, Fleischmann BK, Zaehres H, Schöler HR | title = Oct4-induced pluripotency in adult neural stem cells | journal = Cell | volume = 136 | issue = 3 | pages = 411–9 | date = February 2009 | pmid = 19203577 | doi = 10.1016/j.cell.2009.01.023 | s2cid = 1630949 | doi-access = free }} Moreover, while Sox2, Klf4, and cMyc could be replaced by their respective family members, Oct4's closer relatives, Oct1 and Oct6, fail to induce pluripotency, thus demonstrating the exclusiveness of Oct4 among POU transcription factors.{{cite journal | vauthors = Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S | title = Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts | journal = Nature Biotechnology | volume = 26 | issue = 1 | pages = 101–6 | date = January 2008 | pmid = 18059259 | doi = 10.1038/nbt1374 | s2cid = 1705950 }} However, later it was shown that Oct4 could be completely omitted from the Yamanaka cocktail, and the remaining three factors, Sox2, Klf4, and cMyc (SKM) could generate mouse iPSCs with dramatically enhanced developmental potential.{{cite journal | vauthors = Velychko S, Adachi K, Kim KP, Hou Y, MacCarthy CM, Wu G, Schöler HR | title = Excluding Oct4 from Yamanaka Cocktail Unleashes the Developmental Potential of iPSCs | journal = Cell Stem Cell | volume = 25 | issue = 6 | pages = 737–753.e4 | date = December 2019 | pmid = 31708402 | doi = 10.1016/j.stem.2019.10.002 | pmc = 6900749 | doi-access = free }} This suggests that Oct4 increases the efficiency of reprogramming, but decreases the quality of resulting iPSCs. This is possibly due to a mutated OCT4 DBD cysteine residue (Cys48) that has been identified as a central reprogramming determinant.{{cite journal | vauthors = Shen Z, Wu Y, Manna A, Yi C, Cairns BR, Evason KJ, Chandrasekharan MB, Tantin D | title = Oct4 redox sensitivity potentiates reprogramming and differentiation | journal = Genes & Development | volume = 38 | issue = 7–8 | pages = 308–321 | date = May 2024 | pmid = 38719541 | doi = 10.1101/gad.351411.123 | pmc = 11146590 }} The serine residue in OCT1 is mutated in the presence of the OCT4 N terminus, which conversely causes OCT4's serine (converted from cysteine) to reduce reprogramming efficiency by 60%.

• In in vitro experiments of mouse embryonic stem cells, Oct-4 has often been used as a marker of stemness, as differentiated cells show reduced expression of this marker.
• Oct3/4 can both repress and activate the promoter of Rex1. In cells that already express high level of Oct3/4, exogenously transfected Oct3/4 will lead to the repression of Rex1.{{cite journal | vauthors = Ben-Shushan E, Thompson JR, Gudas LJ, Bergman Y | title = Rex-1, a gene encoding a transcription factor expressed in the early embryo, is regulated via Oct-3/4 and Oct-6 binding to an octamer site and a novel protein, Rox-1, binding to an adjacent site | journal = Molecular and Cellular Biology | volume = 18 | issue = 4 | pages = 1866–78 | date = April 1998 | pmid = 9528758 | pmc = 121416 | doi = 10.1128/mcb.18.4.1866 }} However, in cells that are not actively expressing Oct3/4, exogenous transfection of Oct3/4 will lead to the activation of Rex1. This implies a dual regulatory ability of Oct3/4 on Rex1. At low levels of the Oct3/4 protein, the Rex1 promoter is activated, while at high levels of the Oct3/4 protein, the Rex1 promoter is repressed.
• Oct4 contributes to the rapid cell cycle of ESCs by promoting progression through the G1 phase, specifically through transcriptional inhibition of cyclin-dependent kinase inhibitors such as p21.{{cite journal | vauthors = Lee J, Go Y, Kang I, Han YM, Kim J | title = Oct-4 controls cell-cycle progression of embryonic stem cells | journal = The Biochemical Journal | volume = 426 | issue = 2 | pages = 171–81 | date = February 2010 | pmid = 19968627 | pmc = 2825734 | doi = 10.1042/BJ20091439 }}
• CRISPR-Cas9 knockout of the gene in human embryonic stem cells demonstrated that Oct-4 is essential for the development after fertilisation.{{cite journal | vauthors = Fogarty NM, McCarthy A, Snijders KE, Powell BE, Kubikova N, Blakeley P, Lea R, Elder K, Wamaitha SE, Kim D, Maciulyte V, Kleinjung J, Kim JS, Wells D, Vallier L, Bertero A, Turner JM, Niakan KK | title = Genome editing reveals a role for OCT4 in human embryogenesis | journal = Nature | volume = 550 | issue = 7674 | pages = 67–73 | date = October 2017 | pmid = 28953884 | pmc = 5815497 | doi = 10.1038/nature24033 | bibcode = 2017Natur.550...67F }}
• Oct3/4 represses Suv39h1 expression through the activation of an antisense long non-coding RNA. Suv39h1 inhibition maintains low level of H3K9me3 in pluripotent cells limiting the formation of heterochromatin.{{cite journal | vauthors = Bernard LD, Dubois A, Heurtier V, Fischer V, Gonzalez I, Chervova A, Tachtsidi A, Gil N, Owens N, Bates LE, Vandormael-Pournin S, Silva JC, Ulitsky I, Cohen-Tannoudji M, Navarro P | title = OCT4 activates a Suv39h1-repressive antisense lncRNA to couple histone H3 Lysine 9 methylation to pluripotency | journal = Nucleic Acids Research | volume = 50 | issue = 13 | pages = 7367–7379 | date = July 2022 | pmid = 35762231 | pmc = 9303268 | doi = 10.1093/nar/gkac550 }}

Several studies suggest a role for Oct-4 in sustaining self-renewal capacity of adult somatic stem cells (i.e. stem cells from epithelium, bone marrow, liver, etc.).For example:

• {{cite journal | vauthors = Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK, Trosko JE | title = Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis | journal = Carcinogenesis | volume = 26 | issue = 2 | pages = 495–502 | date = February 2005 | pmid = 15513931 | doi = 10.1093/carcin/bgh321 | doi-access = free }}
• {{cite journal | vauthors = Kim JH, Jee MK, Lee SY, Han TH, Kim BS, Kang KS, Kang SK | title = Regulation of adipose tissue stromal cells behaviors by endogenic Oct4 expression control | journal = PLOS ONE | volume = 4 | issue = 9 | pages = e7166 | date = September 2009 | pmid = 19777066 | pmc = 2747014 | doi = 10.1371/journal.pone.0007166 | bibcode = 2009PLoSO...4.7166K | veditors = Mei L | doi-access = free }} Other scientists have produced evidence to the contrary,{{cite journal | vauthors = Lengner CJ, Camargo FD, Hochedlinger K, Welstead GG, Zaidi S, Gokhale S, Scholer HR, Tomilin A, Jaenisch R | title = Oct4 expression is not required for mouse somatic stem cell self-renewal | journal = Cell Stem Cell | volume = 1 | issue = 4 | pages = 403–15 | date = October 2007 | pmid = 18159219 | pmc = 2151746 | doi = 10.1016/j.stem.2007.07.020 }} and dismiss those studies as artifacts of in vitro culture, or interpreting background noise as signal,{{cite journal | vauthors = Lengner CJ, Welstead GG, Jaenisch R | title = The pluripotency regulator Oct4: a role in somatic stem cells? | journal = Cell Cycle | volume = 7 | issue = 6 | pages = 725–8 | date = March 2008 | pmid = 18239456 | doi = 10.4161/cc.7.6.5573 | url = http://www.landesbioscience.com/journals/cc/article/5573/ | doi-access = free }} and warn about Oct-4 pseudogenes giving false detection of Oct-4 expression.{{cite journal | vauthors = Zangrossi S, Marabese M, Broggini M, Giordano R, D'Erasmo M, Montelatici E, Intini D, Neri A, Pesce M, Rebulla P, Lazzari L | title = Oct-4 expression in adult human differentiated cells challenges its role as a pure stem cell marker | journal = Stem Cells | volume = 25 | issue = 7 | pages = 1675–80 | date = July 2007 | pmid = 17379765 | doi = 10.1634/stemcells.2006-0611 | s2cid = 23662657 | doi-access = free }}

Oct-4 has also been implicated as a marker of cancer stem cells.{{cite journal | vauthors = Kim RJ, Nam JS | title = OCT4 Expression Enhances Features of Cancer Stem Cells in a Mouse Model of Breast Cancer | journal = Laboratory Animal Research | volume = 27 | issue = 2 | pages = 147–52 | date = June 2011 | pmid = 21826175 | pmc = 3145994 | doi = 10.5625/lar.2011.27.2.147 }}{{cite journal | vauthors = Atlasi Y, Mowla SJ, Ziaee SA, Bahrami AR | title = OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer | journal = International Journal of Cancer | volume = 120 | issue = 7 | pages = 1598–602 | date = April 2007 | pmid = 17205510 | doi = 10.1002/ijc.22508 | s2cid = 23516214 | doi-access = free }}

A majority of Oct4 cancer stem-like cell studies (CSC) report a positive association between expression of OCT4 and chemoresistance.{{cite journal | vauthors = Mohiuddin IS, Wei SJ, Kang MH | title = Role of OCT4 in cancer stem-like cells and chemotherapy resistance | journal = Biochimica et Biophysica Acta. Molecular Basis of Disease | volume = 1866 | issue = 4 | pages = 165432 | date = April 2020 | pmid = 30904611 | pmc = 6754810 | doi = 10.1016/j.bbadis.2019.03.005 }} Chemotherapy resulting in the enrichment of CSCs showed changes in the phenotypes and increased stem cell markers of OCT4.{{cite journal | vauthors = Lee S, Wottrich S, Bonavida B | title = Crosstalks between Raf-kinase inhibitor protein and cancer stem cell transcription factors (Oct4, KLF4, Sox2, Nanog) | journal = Tumour Biology | volume = 39 | issue = 4 | pages = 1010428317692253 | date = April 2017 | pmid = 28378634 | doi = 10.1177/1010428317692253 | doi-access = free }} Various cancers such as lung cancer, bladder cancer, and mesothelioma cells with high OCT4 expressions showed resistance to cisplatin, general drug resistance, and tumor recurrence. Breast cancer patients had tamoxifen resistance and poor clinical outcomes associated with OCT4.{{cite journal | vauthors = Gwak JM, Kim M, Kim HJ, Jang MH, Park SY | title = Expression of embryonal stem cell transcription factors in breast cancer: Oct4 as an indicator for poor clinical outcome and tamoxifen resistance | journal = Oncotarget | volume = 8 | issue = 22 | pages = 36305–36318 | date = May 2017 | pmid = 28422735 | doi = 10.18632/oncotarget.16750 | pmc = 5482656 }}

OCT4 knock-downs increase sensitivity to cisplatin and irradiation in lung cells, retained tumorigenicity in glioma-initiating cells, and metastasis mediation in ovarian cancer. In in vitro studies looking at cisplatin, knock-down of OCT4 increased their sensitivity and reduced cell proliferation. Further investigation is needed due to the sparsity of stem cells within tumors and their heterogeneity.

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• Enhancer
• Histone
• Pribnow box
• RNA polymerase
• Gene regulatory network

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{{Reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Lamoury FM, Croitoru-Lamoury J, Brew BJ | 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 | vauthors = Hough SR, Clements I, Welch PJ, Wiederholt KA | 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 | date = June 2006 | pmid = 16456133 | doi = 10.1634/stemcells.2005-0475 | s2cid = 27609337 | doi-access = free }}
• {{cite journal | vauthors = Feldman N, Gerson A, Fang J, Li E, Zhang Y, Shinkai Y, Cedar H, Bergman Y | title = G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis | journal = Nature Cell Biology | volume = 8 | issue = 2 | pages = 188–94 | date = February 2006 | pmid = 16415856 | doi = 10.1038/ncb1353 | s2cid = 23740530 }}
• {{cite journal | vauthors = Gerrard L, Zhao D, Clark AJ, 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 | s2cid = 21603127 | doi-access = free }}
• {{cite journal | vauthors = Reményi A, Lins K, Nissen LJ, Reinbold R, Schöler HR, Wilmanns M | title = Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers | journal = Genes & Development | volume = 17 | issue = 16 | pages = 2048–59 | date = August 2003 | pmid = 12923055 | pmc = 196258 | doi = 10.1101/gad.269303 }}
• {{cite journal | vauthors = Schoorlemmer J, Kruijer W | title = Octamer-dependent regulation of the kFGF gene in embryonal carcinoma and embryonic stem cells | journal = Mechanisms of Development | volume = 36 | issue = 1–2 | pages = 75–86 | date = December 1991 | pmid = 1723621 | doi = 10.1016/0925-4773(91)90074-G | s2cid = 8353907 }}
• {{cite journal | vauthors = Wey E, Lyons GE, Schäfer BW | title = A human POU domain gene, mPOU, is expressed in developing brain and specific adult tissues | journal = European Journal of Biochemistry | volume = 220 | issue = 3 | pages = 753–62 | date = March 1994 | pmid = 7908264 | doi = 10.1111/j.1432-1033.1994.tb18676.x | doi-access = free }}
• {{cite journal | vauthors = Crouau-Roy B, Amadou C, Bouissou C, Clayton J, Vernet C, Ribouchon MT, Pontarotti P | 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 | date = May 1994 | pmid = 8088794 | doi = 10.1006/geno.1994.1249 }}
• {{cite journal | vauthors = Guillaudeux T, Mattei MG, Depetris D, Le Bouteiller P, Pontarotti P | title = In situ hybridization localizes the human OTF3 to chromosome 6p21.3→p22 and OTF3L to 12p13 | journal = Cytogenetics and Cell Genetics | volume = 63 | issue = 4 | pages = 212–4 | year = 1993 | pmid = 8500351 | doi = 10.1159/000133537 }}
• {{cite journal | vauthors = Abdel-Rahman B, Fiddler M, Rappolee D, Pergament E | title = Expression of transcription regulating genes in human preimplantation embryos | journal = Human Reproduction | volume = 10 | issue = 10 | pages = 2787–92 | date = October 1995 | pmid = 8567814 | doi = 10.1093/oxfordjournals.humrep.a135792 }}
• {{cite journal | vauthors = Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, Dietrich N, DuBuque T, Favello A, Gish W, Hawkins M, Hultman M, Kucaba T, Lacy M, Le M, Le N, Mardis E, Moore B, Morris M, Parsons J, Prange C, Rifkin L, Rohlfing T, Schellenberg K, Bento Soares M, Tan F, Thierry-Meg J, Trevaskis E, Underwood K, Wohldman P, Waterston R, Wilson R, Marra M | title = Generation and analysis of 280,000 human expressed sequence tags | journal = Genome Research | volume = 6 | issue = 9 | pages = 807–28 | date = September 1996 | pmid = 8889549 | doi = 10.1101/gr.6.9.807 | doi-access = free }}
• {{cite journal | vauthors = Inamoto S, Segil N, Pan ZQ, Kimura M, Roeder RG | 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 = The Journal of Biological Chemistry | volume = 272 | issue = 47 | pages = 29852–8 | date = November 1997 | pmid = 9368058 | doi = 10.1074/jbc.272.47.29852 | doi-access = free }}
• {{cite journal | vauthors = Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Schöler H, Smith A | 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 | date = October 1998 | pmid = 9814708 | doi = 10.1016/S0092-8674(00)81769-9 | s2cid = 12892299 | doi-access = free }}
• {{cite journal | vauthors = Gonzalez MI, Robins DM | title = Oct-1 preferentially interacts with androgen receptor in a DNA-dependent manner that facilitates recruitment of SRC-1 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 9 | pages = 6420–8 | date = March 2001 | pmid = 11096094 | doi = 10.1074/jbc.M008689200 | doi-access = free }}
• {{cite journal | vauthors = 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 = Journal of Molecular Biology | volume = 304 | issue = 4 | pages = 529–40 | date = December 2000 | pmid = 11099378 | doi = 10.1006/jmbi.2000.4238 }}
• {{cite journal | vauthors = Ezashi T, Ghosh D, Roberts RM | title = Repression of Ets-2-induced transactivation of the tau interferon promoter by Oct-4 | journal = Molecular and Cellular Biology | volume = 21 | issue = 23 | pages = 7883–91 | date = December 2001 | pmid = 11689681 | pmc = 99954 | doi = 10.1128/MCB.21.23.7883-7891.2001 }}
• {{cite journal | vauthors = Guo Y, Costa R, Ramsey H, Starnes T, Vance G, Robertson K, Kelley M, Reinbold R, Scholer H, Hromas R | title = The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 6 | pages = 3663–7 | date = March 2002 | pmid = 11891324 | pmc = 122580 | doi = 10.1073/pnas.062041099 | bibcode = 2002PNAS...99.3663G | doi-access = free }}
• {{cite journal | vauthors = Looijenga LH, Stoop H, de Leeuw HP, de Gouveia Brazao CA, Gillis AJ, van Roozendaal KE, van Zoelen EJ, Weber RF, Wolffenbuttel KP, van Dekken H, Honecker F, Bokemeyer C, Perlman EJ, Schneider DT, Kononen J, Sauter G, Oosterhuis JW | title = POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors | journal = Cancer Research | volume = 63 | issue = 9 | pages = 2244–50 | date = May 2003 | pmid = 12727846 }}
• {{cite journal | vauthors = Wang P, Branch DR, Bali M, Schultz GA, Goss PE, Jin T | title = The POU homeodomain protein OCT3 as a potential transcriptional activator for fibroblast growth factor-4 (FGF-4) in human breast cancer cells | journal = The Biochemical Journal | volume = 375 | issue = Pt 1 | pages = 199–205 | date = October 2003 | pmid = 12841847 | pmc = 1223663 | doi = 10.1042/BJ20030579 }}
• {{cite journal | vauthors = Reményi A, Lins K, Nissen LJ, Reinbold R, Schöler HR, Wilmanns M | title = Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers | journal = Genes & Development | volume = 17 | issue = 16 | pages = 2048–59 | date = August 2003 | pmid = 12923055 | pmc = 196258 | doi = 10.1101/gad.269303 }}
• {{cite journal | vauthors = Rajpert-De Meyts E, Hanstein R, Jørgensen N, Graem N, Vogt PH, Skakkebaek NE | title = Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads | journal = Human Reproduction | volume = 19 | issue = 6 | pages = 1338–44 | date = June 2004 | pmid = 15105401 | doi = 10.1093/humrep/deh265 | doi-access = free }}
• {{cite journal | vauthors = Matin MM, Walsh JR, Gokhale PJ, Draper JS, Bahrami AR, Morton I, Moore HD, Andrews PW | 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 | s2cid = 35018708 | doi-access = free }}
• {{cite journal | vauthors = Baal N, Reisinger K, Jahr H, Bohle RM, Liang O, Münstedt K, Rao CV, Preissner KT, Zygmunt MT | title = Expression of transcription factor Oct-4 and other embryonic genes in CD133 positive cells from human umbilical cord blood | journal = Thrombosis and Haemostasis | volume = 92 | issue = 4 | pages = 767–75 | date = October 2004 | pmid = 15467907 | doi = 10.1160/TH04-02-0079 | s2cid = 4646923 }}

{{refend}}

• {{MeshName|Oct-4+Transcription+Factor}}
• {{FactorBook|POU5F1}}
• [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] {{Webarchive|url=https://web.archive.org/web/20080409111706/http://www.jove.com/index/details.stp?ID=734 |date=2008-04-09 }}

{{Transcription factors|g3}}

Category:POU-domain proteins