POU4F1
Developmental stage
Expression peaks early in embryogenesis (day 13.5) and is undetectable 14 days after birth.
Domain
The C-terminal domain is able to act as both DNA-binding domain and a transcriptional activator. The N-terminal domain is also required for transactivation activity on some target genes acting as a discrete activation domain. Neurite outgrowth and expression of genes required for synapse formation are primarily dependent on the C-terminal domain, however the N-terminal domain is required for maximal induction.
Function
Multifunctional transcription factor with different regions mediating its different effects. Acts by binding (via its C-terminal domain) to sequences related to the consensus octamer motif 5'-ATGCAAAT-3' in the regulatory regions of its target genes. Regulates the expression of specific genes involved in differentiation and survival within a subset of neuronal lineages. It has been shown that activation of some of these genes requires its N-terminal domain, maybe through a neuronal-specific cofactor. Activates BCL2 expression and protects neuronal cells from apoptosis (via the N-terminal domain). Induces neuronal process outgrowth and the coordinate expression of genes encoding synaptic proteins. Exerts its major developmental effects in somatosensory neurons and in brainstem nuclei involved in motor control. Stimulates the binding affinity of the nuclear estrogene receptor ESR1 to DNA estrogen response element (ERE), and hence modulates ESR1-induced transcriptional activity. May positively regulate POU4F2 and POU4F3. Regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord. Plays a role in TNFSF11-mediated terminal osteoclast differentiation. Negatively regulates its own expression interacting directly with a highly conserved autoregulatory domain surrounding the transcription initiation site.
Isoform 2
Able to act as transcription factor, cannot regulate the expression of the same subset of genes than isoform 1. Does not have antiapoptotic effect on neuronal cells.
Involvement in disease
Ataxia, intention tremor, and hypotonia syndrome, childhood-onset
ATITHS
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, mildly impaired intellectual development with speech delay or learning disabilities, delayed walking due to ataxia, intention tremor, and hypotonia apparent from early childhood. Brain imaging shows cerebellar atrophy in some patients.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the POU transcription factor family. Class-4 subfamily.
Tissue Specificity
Expressed in the brain and the retina. Present in the developing brain, spinal cord and eye.
Cellular localization
- Nucleus
- Cytoplasm
Alternative names
BRN3A, RDC1, POU4F1, Brain-specific homeobox/POU domain protein 3A, Homeobox/POU domain protein RDC-1, Oct-T1, Brain-3A, Brn-3A