POU domain, class 4, transcription factor 1 (POU4F1) also known as brain-specific homeobox/POU domain protein 3A (BRN3A), homeobox/POU domain protein RDC-1 or Oct-T1 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''POU4F1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
BRN3A (POU4F1) is a class IV
POU domain-containing
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
highly expressed in the developing peripheral sensory nervous system (
dorsal root ganglia
A dorsal root ganglion (or spinal ganglion; also known as a posterior root ganglion) is a cluster of neurons (a ganglion) in a dorsal root of a spinal nerve. The cell bodies of sensory neurons known as first-order neurons are located in the dors ...
,
trigeminal ganglion
The trigeminal ganglion (also known as: Gasserian ganglion, semilunar ganglion, or Gasser's ganglion) is the sensory ganglion of each trigeminal nerve (CN V). The trigeminal ganglion is located within the trigeminal cave (Meckel's cave), a cav ...
, and
hindbrain
The hindbrain, rhombencephalon (shaped like a rhombus) is a developmental categorization of portions of the central nervous system in vertebrates. It includes the medulla, pons, and cerebellum. Together they support vital bodily processes.
Met ...
sensory ganglia), certain regions of the central nervous system, retinal neurons called ganglion cells, and in cells of the B- and T-lymphocytic lineages.
Discovery
Brn3a was initially discovered in mice based on homology to the prototypal POU transcription factors Pit1 (
Pituitary-specific positive transcription factor 1, Pou1f1), Oct1 (
Pou2f1
POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the ''POU2F1'' gene.
Interactions
POU2F1 has been shown to interact with:
* EPRS,
* Glucocorticoid receptor,
* Glyceraldehyde 3-phosphate dehydrogenase, ...
), and the Caenorhabditis elegans factor Unc86, and named Brn3.
When multiple members of the Brn3 gene class were discovered, it was renamed Brn3.0 and Brn3a by different groups of researchers.
Subsequently, the gene was systematically renamed ''Pou4f1'' in mice and ''POU4F1'' in humans. The protein product is still frequently referred to as Brn3a.
Function
In addition to sensory neurons, in rodents and birds (and presumably humans) Brn3a is expressed in multiple sites in the central nervous system, including the spinal cord, midbrain superior colliculus,
red nucleus
The red nucleus or nucleus ruber is a structure in the rostral midbrain involved in motor coordination. The red nucleus is pale pink, which is believed to be due to the presence of iron in at least two different forms: hemoglobin and ferritin. ...
,
nucleus ambiguus
The nucleus ambiguus ("ambiguous nucleus" in English) is a group of large motor neurons, situated deep in the medullary part of the reticular formation named by Jacob Clarke. The nucleus ambiguus contains the cell bodies of neurons that innerva ...
,
inferior olivary nucleus
The inferior olivary nucleus (ION) is a structure found in the medulla oblongata underneath the superior olivary nucleus.Gado, Thomas A. Woolsey; Joseph Hanaway; Mokhtar H. (2003). The brain atlas a visual guide to the human central nervous syste ...
,
habenula, and retina.
Mice with null mutations ("knockouts") in Brn3a die at birth, due to developmental defects in the nucleus ambiguus, which is essential for respiration.
Brn3a is a transcription factor which acts in development by regulating downstream "target" genes. Microarrays have been used to determine many genes downstream of Brn3a in peripheral sensory neurons.
In the sensory neurons Brn3a is co-expressed with the
LIM domain
LIM domains are protein structural domains, composed of two contiguous zinc fingers, separated by a two-amino acid residue hydrophobic linker. The domain name is an acronym of the three genes in which it was first identified (LIN-11, Isl-1 and M ...
transcription factor
ISL1 or Islet1, and has many downstream targets in common with Isl1.
Pou4f1/Isl1 double mutant mice show strong epistatic effects in regulation of many downstream genes in the sensory neurons of double mutant mouse embryos.
Although the homozygous Brn3a null mutation is lethal at birth in mice, Brn3a null heterozygotes have no known phenotype. i.e. the Brn3a null mutation is completely recessive. This can be explained by gene dosage compensation due to autoregulation,
in which expression of the remaining copy of the Pou4f1 gene is increased in heterozygotes, leading to near-normal expression of its downstream targets.
The combination of homozygote lethality and dosage compensation in heterozygotes may explain why POU4F1 mutations have not been identified in any human disease, whereas diseases are associated with several other members of the POU domain transcription factor class.
Interactions
POU4F1 has been shown to
interact with
Estrogen receptor alpha
Estrogen receptor alpha (ERĪ±), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein)
that is activated by the sex ...
,
and
Ewing sarcoma breakpoint region 1.
See also
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BRN-3
References
Further reading
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External links
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{{Transcription factors, g3
POU-domain proteins