Oct-4

For the day, see October 4.

"Oct-3" redirects here. For the day, see October 3.

POU class 5 homeobox 1
Identifiers
Symbols	POU5F1 ; OCT3; OCT4; OTF-3; OTF3; OTF4; Oct-3; Oct-4
External IDs	OMIM: 164177 MGI: 101893 HomoloGene: 8422 GeneCards: POU5F1 Gene
Gene ontology Molecular function • transcription regulatory region sequence-specific DNA binding • RNA polymerase II transcription factor activity, sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding • DNA binding • transcription factor activity, sequence-specific DNA binding • protein binding • transcription factor binding • ubiquitin protein ligase binding • miRNA binding • sequence-specific DNA binding • transcription regulatory region DNA binding • poly(A) RNA binding Cellular component • nucleus • nucleoplasm • transcription factor complex • cytoplasm • cytosol Biological process • negative regulation of transcription from RNA polymerase II promoter • endodermal cell fate specification • blastocyst development • BMP signaling pathway involved in heart induction • regulation of transcription, DNA-templated • transcription from RNA polymerase II promoter • response to wounding • anatomical structure morphogenesis • regulation of asymmetric cell division • regulation of gene expression • somatic stem cell maintenance • positive regulation of catenin import into nucleus • mRNA transcription from RNA polymerase II promoter • positive regulation of transcription from RNA polymerase II promoter • positive regulation of SMAD protein import into nucleus • cell fate commitment involved in formation of primary germ layer • cardiac cell fate determination • negative regulation of gene silencing by miRNA • regulation of heart induction by regulation of canonical Wnt signaling pathway • regulation of methylation-dependent chromatin silencing Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5460	18999
Ensembl	ENSG00000204531	ENSMUSG00000024406
UniProt	Q01860	P20263
RefSeq (mRNA)	NM_001173531	NM_001252452
RefSeq (protein)	NP_001167002	NP_001239381
Location (UCSC)	Chr 6: 31.16 – 31.18 Mb	Chr 17: 35.51 – 35.51 Mb
PubMed search	[1]	[2]

Oct-4 (octamer-binding transcription factor 4) also known as POU5F1 (POU domain, class 5, transcription factor 1) is a protein that in humans is encoded by the POU5F1 gene. Oct-4 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 cause differentiation of the cells.

The octamer (made of eight units) in this family of transcription factors is the DNA nucleotide sequence "ATTTGCAT", the etymology for the naming of the octamer transcription factor.

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. Gene knockdown of Oct-4 promotes differentiation, thereby demonstrating a role for these factors in human embryonic stem cell self-renewal. Oct-4 can form a heterodimer with Sox2, so that these two proteins bind DNA together.

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

Orthologs of Oct-4 exist in humans and several other species including:

Species	Entrez GeneID	Chromosome	Location	RefSeq (mRNA)	RefSeq (protein)
Mus musculus	18999	17,17 B1; 17 19.23 cM	NC_000083.4, 35114104..35118822 (Plus Strand)	NM_013633.1	NP_038661.1
Homo sapiens	5460	6, 6p21.31	NC_000006.10, 31246432-31240107 (Minus Strand)	NM_002701.3	NP_002692.2 (full length isoform) NP_002692.1 (N-terminal truncated isoform)
Rattus norvegicus	294562	20	NW_001084776, 650467-655015 (Minus strand)	NM_001009178	NP_001009178
Danio rerio (Zebrafish)	303333	21	NC_007127.1, 27995548-28000317 (Minus strand)	NM_131112	NP_571187

Structural Information

Oct-4 contains the following protein domains:

Domain	Description	Length (AA)
POU domain	Found in Pit-Oct-Unc transcription factors	75
Homeodomain	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.	59

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.

Pluripotency in embryo development

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 stem 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.

The transcription factors Oct-4, Sox2 and Nanog are capable of inducing the expression of each other, and are essential for maintaining the self-renewing undifferentiated state of the inner cell mass of the blastocyst, as well as in embryonic stem cells (which are cell lines derived from the inner cell mass).

Oct-4 is one of the transcription factors used to create induced pluripotent stem cells, together with Sox2, Klf4 and often c-Myc in mouse, demonstrating its capacity to induce an embryonic stem cell-like state. It was later deterimined that only two of these four factors, Oct4 and Klf4 were sufficient to reprogram mouse adult neural stem cells. Finally it was shown that a single factor, Oct-4 was sufficient for this transformation.

In embryonic stem cells

In in-vitro experiments of murine 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 Rex1 promoter. In cells that already express high level of Oct3/4, exogenously transfected Oct3/4 will lead to the repression of Rex1. However, in cells that are not actively expressing Oct3/4, an 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.

In adult stem cells

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.). Other scientists have produced evidence to the contrary, and dismiss those studies as artifacts of in vitro culture, or interpreting background noise as signal, and warn about Oct-4 pseudogenes giving false detection of Oct-4 expression. Oct-4 has also been implicated as a marker of cancer stem cells.

See also

• Enhancer
• Histone
• Nanog (transcription factor)
• Pribnow box
• RNA polymerase
• Transcription factors
• Gene regulatory network
• Induced pluripotent stem cells (iPS) Cells

External links

• Oct-4 Transcription Factor at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook POU5F1
• Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4