POU3F2 gene

The POU3F2 gene (POU3F2 stands for POU Class 3 Homeobox 2) is a protein-coding gene located on chromosome 6q16.1. An important paralog of this gene is POU3F3.

The POU3F2 gene encodes a member of the POU-III class of neuronal transcription factors (transcription factor BRN2). BRN2 preferentially binds to the recognition sequence, which consists of two distinct half sites, ('GCAT') and ('TAAT'), separated by a non-conserved spacer region of 0, 2 or 3 nucleotides. BRN2 acts as a transcriptional activator when it binds to gene promoters together with SOX4, SOX11 or SOX12. The combination of the three transcription factors ASCL1, POU3F2/BRN2 and MYT1L is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro. BRN2 acts downstream of ASCL1, accessing chromatin opened by ASCL1 and promoting transcription of neuronal genes.

Overexpression of BRN2 is associated with an increase in melanoma cell proliferation. It has also been shown that there is a negative correlation between the degree of differentiation of melanocytes and BRN2 expression. Human melanoblasts isolated from neonatal foreskin and cultured in a medium containing fibroblast growth factor-2 (FGF-2), stem cell factor (SCF) and endothelin-3 (ET-3) showed relatively high BRN2 expression in various studies. In various studies, BRN2 expression was relatively high, whereas it decreased in a medium without FGF-2, SCF and ET-3 with increasing pigmentation and differentiation into melanocytes. When melanocytes were cultured in a medium with the addition of FGF-2, SCF and ET-3, a decrease in cell pigmentation and an increase in BRN2 expression was observed (Cook et al. 2003).

Diseases associated with POU3F2 include microphthalmia and melanoma.

1. Ding C et al. (2021) Transcription factor POU3F2 regulates TRIM8 expression contributing to cellular functions implicated in schizophrenia. Mol Psychiatry 26:3444-3460.
2. Wang Z et al. (2022) Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer. iScience 25:104576.