Oct-4
Encyclopedia
Oct-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 cell
s. 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.
, 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.
s:
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 cell
s (which are cell lines derived from the inner cell mass).
Oct-4 is one of the transcription factors used to create induced pluripotent stem cell
s, 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.
(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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the POU5F1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Oct-4 is a homeodomain transcription factor
Homeobox
A homeobox is a DNA sequence found within genes that are involved in the regulation of patterns of anatomical development in animals, fungi and plants.- Discovery :...
of the POU family. This protein is critically involved in the self-renewal of undifferentiated embryonic stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s. As such, it is frequently used as a marker
Biomarker (cell)
A biomarker can be understood as a molecule that is present from a particular cellular type. This facilitates the characterization of a cell type, their identification, and eventually their isolation. Cell sorting techniques are based on cellular biomarkers...
for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will actually cause differentiation of the cells.
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. In fact 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 Sox2SOX2
SRY -box 2, also known as SOX2, is a transcription factor that is essential to maintain self-renewal of undifferentiated embryonic stem cells....
, 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 Danio rerio The zebrafish, Danio rerio, is a tropical freshwater fish belonging to the minnow family of order Cypriniformes. It is a popular aquarium fish, frequently sold under the trade name zebra danio, and is an important vertebrate model organism in scientific research.-Taxonomy:The zebrafish are... |
303333 | 21 | NC_007127.1, 27995548-28000317 (Minus strand) | NM_131112 | NP_571187 |
Structural Information
Oct-4 contains the following protein domainProtein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
s:
| Domain | Description | Length (AA) |
|---|---|---|
| POU domain POU domain POU is a family of proteins that have well-conserved homeodomains.-Etymology:The acronym POU is derived from the names of three transcription factors:* the Pituitary-specific Pit-1... |
Found in Pit-Oct-Unc transcription factors | 75 |
| Homeodomain Homeodomain fold The homeodomain fold is a protein structural domain that binds DNA or RNA and is thus commonly found in transcription factors. The fold consists of a 60-amino acid helix-turn-helix structure in which three alpha helices are connected by short loop regions... |
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.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
Inner cell mass
In early embryogenesis of most eutherian mammals, the inner cell mass is the mass of cells inside the primordial embryo that will eventually give rise to the definitive structures of the fetus...
of the blastocyst, as well as in embryonic stem cell
Embryonic stem cell
Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells...
s (which are cell lines derived from the inner cell mass).
Oct-4 is one of the transcription factors used to create induced pluripotent stem cell
Induced pluripotent stem cell
Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of specific genes....
s, together with Sox2
SOX2
SRY -box 2, also known as SOX2, is a transcription factor that is essential to maintain self-renewal of undifferentiated embryonic stem cells....
, Klf4
Kruppel-like factors
The Krüppel-like family of transcription factors , so named for their homology to the Drosophila melanogaster Krüppel protein, have been extensively studied for their roles in cell proliferation, differentiation and survival, especially in the context of cancer . All KLF family members are...
and often c-Myc
Myc
Myc is a regulator gene that codes for a transcription factor. In the human genome, Myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes through binding on Enhancer Box sequences and recruiting histone acetyltransferases...
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 adult stem cells
Several studies suggest a role for Oct-4 in sustaining self-renewal capacity of adult somatic stem cellsAdult stem cell
Adult stem cells are undifferentiated cells, found throughout the body after embryonic development, that multiply by cell division to replenish dying cells and regenerate damaged tissues...
(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.
See also
- EnhancerEnhancer (genetics)In genetics, an enhancer is a short region of DNA that can be bound with proteins to enhance transcription levels of genes in a gene cluster...
- HistoneHistoneIn biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
- Nanog (transcription factor)Nanog (transcription factor)NANOG is a transcription factor critically involved with self-renewal of undifferentiated embryonic stem cells. In humans, this protein is encoded by the NANOG gene.- Structure :...
- Pribnow boxPribnow boxThe Pribnow box is the sequence TATAAT of six nucleotides that is an essential part of a promoter site on DNA for transcription to occur in bacteria...
- Promoter
- RNA polymeraseRNA polymeraseRNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
- Transcription factors
- Gene regulatory networkGene regulatory networkA gene regulatory network or genetic regulatory network is a collection of DNA segments in a cell whichinteract with each other indirectly and with other substances in the cell, thereby governing the rates at which genes in the network are transcribed into mRNA.In general, each mRNA molecule goes...
- BioinformaticsBioinformaticsBioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
- Induced pluripotent stem cells (iPS) CellsInduced pluripotent stem cellInduced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of specific genes....