POU4F1

Source: Wikipedia, the free encyclopedia.
POU4F1
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_006237

NM_011143

RefSeq (protein)

NP_006228

NP_035273

Location (UCSC)Chr 13: 78.6 – 78.6 Mbn/a
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

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 that in humans is encoded by the POU4F1 gene.[4][5]

BRN3A (POU4F1) is a class IV

dorsal root ganglia, trigeminal ganglion, and hindbrain sensory ganglia), certain regions of the central nervous system, retinal neurons called ganglion cells, and in cells of the B- and T-lymphocytic lineages.[5][6]

Discovery

Brn3a was initially discovered in mice based on homology to the prototypal POU transcription factors Pit1 (

Pou2f1), and the Caenorhabditis elegans factor Unc86, and named Brn3.[7] When multiple members of the Brn3 gene class were discovered, it was renamed Brn3.0 and Brn3a by different groups of researchers.[6][8]
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, nucleus ambiguus, inferior olivary nucleus, habenula, and retina.[9]

Mice with null mutations ("knockouts") in Brn3a die at birth, due to developmental defects in the nucleus ambiguus, which is essential for respiration.[10][11][12]

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.[13][14]

In the sensory neurons Brn3a is co-expressed with the LIM domain transcription factor ISL1 or Islet1, and has many downstream targets in common with Isl1.[15] Pou4f1/Isl1 double mutant mice show strong epistatic effects in regulation of many downstream genes in the sensory neurons of double mutant mouse embryos.[16]

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,[17] in which expression of the remaining copy of the Pou4f1 gene is increased in heterozygotes, leading to near-normal expression of its downstream targets.[13] 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

Ewing sarcoma breakpoint region 1.[20]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000152192 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. PMID 1357630
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  5. ^ a b "Entrez Gene: POU4F1 POU domain, class 4, transcription factor 1".
  6. ^
    PMID 8248179
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Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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