POU3F2 (POU class 3 homeobox 2)

2014-04-01   Takuya Yazawa 

Department 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

Atlas Image
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

Atlas Image
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).

Bibliography

Pubmed IDLast YearTitleAuthors
76083431995Model of forebrain regionalization based on spatiotemporal patterns of POU-III homeobox gene expression, birthdates, and morphological features.Alvarez-Bolado G et al
218023862011Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions.Ambasudhan R et al
111598142001POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease.Andersen B et al
212157072011Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A.Arozarena I et al
151782472004Characteristic patterns of N Oct-3 binding to a set of neuronal promoters.Blaud M et al
189835362008POU domain transcription factors: BRN2 as a regulator of melanocytic growth and tumourigenesis.Cook AL et al
228924272013POU-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
230699402012BRN2 is a transcriptional repressor of CDH13 (T-cadherin) in melanoma cells.Ellmann L et al
150240802004The Brn-2 transcription factor links activated BRAF to melanoma proliferation.Goodall J et al
235305602013POU 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
223084652012Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells.Lujan E et al
85431551995The 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
216176442011Induction of human neuronal cells by defined transcription factors.Pang ZP et al
104070361999Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear.Phippard D et al
91713671997POU domain family values: flexibility, partnerships, and developmental codes.Ryan AK et al
233581122013Neural lineage-specific homeoprotein BRN2 is directly involved in TTF1 expression in small-cell lung cancer.Sakaeda M et al
85431561995Development and survival of the endocrine hypothalamus and posterior pituitary gland requires the neuronal POU domain factor Brn-2.Schonemann MD et al
13275241992Human small cell lung cancer expresses the octamer DNA-binding and nervous system-specific transcription factor N-Oct 3 (brain-2).Schreiber E et al
154568592004Interplay of SOX and POU factors in regulation of the Nestin gene in neural primordial cells.Tanaka S et al
76517331995The 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 IDTranscript IDUniprot
ENSG00000184486ENST00000328345P20265

Expression (GTEx)

0
5
10
15

References

Pubmed IDYearTitleCitations
190231252009A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype.104
188295332008Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells.63
277847082017The Master Neural Transcription Factor BRN2 Is an Androgen Receptor-Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer.59
214351932011Melanoma cell invasiveness is regulated by miR-211 suppression of the BRN2 transcription factor.57
150240802004The Brn-2 transcription factor links activated BRAF to melanoma proliferation.36
213586742011Inverse expression states of the BRN2 and MITF transcription factors in melanoma spheres and tumour xenografts regulate the NOTCH pathway.32
281190612017NFIB Mediates BRN2 Driven Melanoma Cell Migration and Invasion Through Regulation of EZH2 and MITF.20
203379852010Genome-wide analysis of POU3F2/BRN2 promoter occupancy in human melanoma cells reveals Kitl as a novel regulated target gene.19
189234472009SOX9 and SOX10 but not BRN2 are required for nestin expression in human melanoma cells.15
229882972012A phosphatidylinositol 3-kinase-Pax3 axis regulates Brn-2 expression in melanoma.14

Citation

Takuya Yazawa

POU3F2 (POU class 3 homeobox 2)

Atlas Genet Cytogenet Oncol Haematol. 2014-04-01

Online version: http://atlasgeneticsoncology.org/gene/45747/pou3f2