POU3F2 (POU class 3 homeobox 2)
2014-04-01 Takuya Yazawa AffiliationDepartment of Surgical Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba 230-8670, Japan
Identity
HGNC
LOCATION
6q16.1
LOCUSID
ALIAS
BRN2,N-Oct3,OCT7,OTF-7,OTF7,POUF3,brn-2,oct-7
FUSION GENES
Abstract
POU3F2, also known as BRN2, Oct7, and N-Oct3, is a member of the neural cell-specific class III POU domain transcription factors (Ryan and Rosenfeld, 1997). POU3F2-knockout causes the loss of specific neuronal lineages in the endocrine hypothalamus and the subsequent loss of the posterior pituitary gland (Nakai et al., 1995; Schonemann et al., 1995; Alvarez-Bolado et al., 1995). And also, transgenes of POU3F2 and some other few factors converted non-neural cells to neural cells in vitro (Ambasudhan et al., 2011; Lujan et al., 2012; Pang et al., 2011). These results indicate that POU3F2 is an indispensable transcription factor for neural differentiation and generation of normal nervous system, especially hypothalamus. There have been a few reports regarding the functions of POU3F2 in association with tumorigenesis. POU3F2 has been demonstrated to be an oncogene in malignant melanomas derived from the neuroectodermal cell lineage and to accelerate the growth of melanoma cells (Cook and Sturm, 2008). POU3F2 are also highly expressed in small cell lung cancers and closely associated with the cancer specific neural\/neuroendocrine phenotype (Schreiber et al., 1992; Ishii et al., 2013; Sakaeda et al., 2013).
DNA/RNA
Schematic representation of POU3F2 gene and mRNA. The POU3F2 gene is located on the plus strand of 6q16.1 chromosome. It consists of one exon (4086 bp).
Description
POU3F2 is intron-less gene. Coding region is located in 5 side of the gene.
Transcription
4108 base mRNA, coding sequence is 1332 base. There are no reports about transcriptional variant.
Proteins
Schematic illustrating POU3F2 protein. POU3F2 has poly-glycine and glutamic acid repeat in N-terminal side and POU-specific domain and homeodomain in C-terminal side.
Description
POU3F2 belongs to the Class-III POU transcription factor family. All class-III POUs mainly express in some part of nervous system and regulate the development (Dominguez et al., 2013; Phippard et al., 1999). Two DNA binding domain, POU-specific domain, and homeodomain are conserved in POU transcription factor family.
Expression
POU3F2 expresses in developing nervous system and hypothalamus (Andersen and Rosenfeld, 2001). It also localizes in the developing mouse spinal cord (Tanaka et al., 2004).
Localisation
POU3F2 mainly localizes in nuclei.
Function
POU3F2 makes homodimer or heterodimer with other transcription factor and recognize specific DNA motif. POU3F2 activates the transcription of near gene. It is reported that target genes of POU3F2 are some neural genes (Blaud et al., 2004), phosphodiesterase 5A (Arozarena et al., 2011), cadherin 13 (Ellmann et al., 2012), NKX2.1 (Sakaeda et al., 2013).
Homology
POU3F2 shows highly similarity with the other class-III POU proteins (POU3F1, POU3F3, POU3F4) especially in the DNA binding domain.
Mutations
Note
There is no report about mutation of POU3F2.
Implicated in
Entity name
Melanoma
Note
POU3F2 is highly expressed in melanoma cells and is related to the tumorigenesis and the growth (Cook and Sturm, 2008). Suppression of POU3F2 reduced proliferation activity and tumorigenic potential of melanoma cells (Thomson et al., 1995). It is reported that high POU3F2 expression is due to the activation of MAPK signaling pathway associated with BRAF gene mutation (Goodall et al., 2004).
Entity name
Small cell lung cancer
Note
Small cell lung cancer (SCLC) highly expresses POU3F2 compared with non-SCLC. POU3F2 induces several neuroendocrine specific transcription factors and marker molecules and is associated to the cell viability (Schreiber et al., 1992; Ishii et al., 2013; Sakaeda et al., 2013).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 7608343 | 1995 | Model of forebrain regionalization based on spatiotemporal patterns of POU-III homeobox gene expression, birthdates, and morphological features. | Alvarez-Bolado G et al |
| 21802386 | 2011 | Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. | Ambasudhan R et al |
| 11159814 | 2001 | POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease. | Andersen B et al |
| 21215707 | 2011 | Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A. | Arozarena I et al |
| 15178247 | 2004 | Characteristic patterns of N Oct-3 binding to a set of neuronal promoters. | Blaud M et al |
| 18983536 | 2008 | POU domain transcription factors: BRN2 as a regulator of melanocytic growth and tumourigenesis. | Cook AL et al |
| 22892427 | 2013 | POU-III transcription factors (Brn1, Brn2, and Oct6) influence neurogenesis, molecular identity, and migratory destination of upper-layer cells of the cerebral cortex. | Dominguez MH et al |
| 23069940 | 2012 | BRN2 is a transcriptional repressor of CDH13 (T-cadherin) in melanoma cells. | Ellmann L et al |
| 15024080 | 2004 | The Brn-2 transcription factor links activated BRAF to melanoma proliferation. | Goodall J et al |
| 23530560 | 2013 | POU domain transcription factor BRN2 is crucial for expression of ASCL1, ND1 and neuroendocrine marker molecules and cell growth in small cell lung cancer. | Ishii J et al |
| 22308465 | 2012 | Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. | Lujan E et al |
| 8543155 | 1995 | The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse. | Nakai S et al |
| 21617644 | 2011 | Induction of human neuronal cells by defined transcription factors. | Pang ZP et al |
| 10407036 | 1999 | Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear. | Phippard D et al |
| 9171367 | 1997 | POU domain family values: flexibility, partnerships, and developmental codes. | Ryan AK et al |
| 23358112 | 2013 | Neural lineage-specific homeoprotein BRN2 is directly involved in TTF1 expression in small-cell lung cancer. | Sakaeda M et al |
| 8543156 | 1995 | Development and survival of the endocrine hypothalamus and posterior pituitary gland requires the neuronal POU domain factor Brn-2. | Schonemann MD et al |
| 1327524 | 1992 | Human small cell lung cancer expresses the octamer DNA-binding and nervous system-specific transcription factor N-Oct 3 (brain-2). | Schreiber E et al |
| 15456859 | 2004 | Interplay of SOX and POU factors in regulation of the Nestin gene in neural primordial cells. | Tanaka S et al |
| 7651733 | 1995 | The brn-2 gene regulates the melanocytic phenotype and tumorigenic potential of human melanoma cells. | Thomson JA et al |
Other Information
Locus ID:
NCBI: 5454
MIM: 600494
HGNC: 9215
Ensembl: ENSG00000184486
Variants:
dbSNP: 5454
ClinVar: 5454
TCGA: ENSG00000184486
COSMIC: POU3F2
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000184486 | ENST00000328345 | P20265 |
Expression (GTEx)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38386071 | 2024 | RFX4 is an intrinsic factor for neuronal differentiation through induction of proneural genes POU3F2 and NEUROD1. | 0 |
| 38386071 | 2024 | RFX4 is an intrinsic factor for neuronal differentiation through induction of proneural genes POU3F2 and NEUROD1. | 0 |
| 36843258 | 2023 | Integrin α3 Mediates Stemness and Invasion of Glioblastoma by Regulating POU3F2. | 3 |
| 37207645 | 2023 | Monoallelic intragenic POU3F2 variants lead to neurodevelopmental delay and hyperphagic obesity, confirming the gene's candidacy in 6q16.1 deletions. | 1 |
| 38201271 | 2023 | CREB1 Facilitates GABAergic Neural Differentiation of Human Mesenchymal Stem Cells through BRN2 for Pain Alleviation and Locomotion Recovery after Spinal Cord Injury. | 0 |
| 36843258 | 2023 | Integrin α3 Mediates Stemness and Invasion of Glioblastoma by Regulating POU3F2. | 3 |
| 37207645 | 2023 | Monoallelic intragenic POU3F2 variants lead to neurodevelopmental delay and hyperphagic obesity, confirming the gene's candidacy in 6q16.1 deletions. | 1 |
| 38201271 | 2023 | CREB1 Facilitates GABAergic Neural Differentiation of Human Mesenchymal Stem Cells through BRN2 for Pain Alleviation and Locomotion Recovery after Spinal Cord Injury. | 0 |
| 34958806 | 2022 | Reciprocal Regulation of BRN2 and NOTCH1/2 Signaling Synergistically Drives Melanoma Cell Migration and Invasion. | 2 |
| 35398178 | 2022 | CircPOLR2A Promotes Proliferation and Impedes Apoptosis of Glioblastoma Multiforme Cells by Up-regulating POU3F2 to Facilitate SOX9 Transcription. | 2 |
| 34958806 | 2022 | Reciprocal Regulation of BRN2 and NOTCH1/2 Signaling Synergistically Drives Melanoma Cell Migration and Invasion. | 2 |
| 35398178 | 2022 | CircPOLR2A Promotes Proliferation and Impedes Apoptosis of Glioblastoma Multiforme Cells by Up-regulating POU3F2 to Facilitate SOX9 Transcription. | 2 |
| 32929213 | 2021 | Transcription factor POU3F2 regulates TRIM8 expression contributing to cellular functions implicated in schizophrenia. | 12 |
| 33539344 | 2021 | Transcriptome-wide transmission disequilibrium analysis identifies novel risk genes for autism spectrum disorder. | 11 |
| 34140478 | 2021 | BRN2 is a non-canonical melanoma tumor-suppressor. | 6 |
Citation
Takuya Yazawa
POU3F2 (POU class 3 homeobox 2)
Atlas Genet Cytogenet Oncol Haematol. 2014-04-01
Online version: http://www.atlasgeneticsoncology.org/gene/45747/pou3f2-(pou-class-3-homeobox-2)
