POU4F1

Last updated
POU4F1
Identifiers
Aliases POU4F1 , BRN3A, Oct-T1, RDC-1, brn-3A, POU class 4 homeobox 1, ATITHS
External IDs OMIM: 601632 MGI: 102525 HomoloGene: 21255 GeneCards: POU4F1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_006237

NM_011143

RefSeq (protein)

NP_006228

NP_035273

Location (UCSC) Chr 13: 78.6 – 78.6 Mb n/a
PubMed search [2] [3]
Wikidata
View/Edit Human View/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]

Contents

BRN3A (POU4F1) is a class IV POU domain-containing transcription factor highly expressed in the developing peripheral sensory nervous system (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 (Pituitary-specific positive transcription factor 1, Pou1f1), Oct1 (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 interact with Estrogen receptor alpha, [18] RIT2 [19] and Ewing sarcoma breakpoint region 1. [20]

See also

Related Research Articles

A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and viruses.

Pituitary-specific positive transcription factor 1 Protein-coding gene in the species Homo sapiens

POU domain, class 1, transcription factor 1 , also known as POU1F1, is a transcription factor for growth hormone.

Oct-2 also known as POU domain, class 2, transcription factor 2 is a protein that in humans is encoded by the POU2F2 gene.

BRN-3 is a group of related transcription factors in the POU family. They are also known as class 4 POU domain homeobox proteins.

ATF3 Protein-coding gene in the species Homo sapiens

Cyclic AMP-dependent transcription factor ATF-3 is a protein that, in humans, is encoded by the ATF3 gene.

POU is a family of proteins that have well-conserved homeodomains.

RE1-silencing transcription factor

RE1-Silencing Transcription factor (REST), also known as Neuron-Restrictive Silencer Factor (NRSF), is a protein which in humans is encoded by the REST gene, and acts as a transcriptional repressor. REST is expressly involved in the repression of neural genes in non-neuronal cells. Many genetic disorders have been tied to alterations in the REST expression pattern, including colon and small-cell lung carcinomas found with truncated versions of REST. In addition to these cancers, defects in REST have also been attributed a role in Huntington Disease, neuroblastomas, and the effects of epileptic seizures and ischemia.

POU3F2 Protein-coding gene in the species Homo sapiens

POU domain, class 3, transcription factor 2 is a protein that in humans is encoded by the POU3F2 gene.

GTF3C1

General transcription factor 3C polypeptide 1 is a protein that in humans is encoded by the GTF3C1 gene.

POU4F2 Protein-coding gene in the species Homo sapiens

POU domain, class 4, transcription factor 2 is a protein that in humans is encoded by the POU4F2 gene.

POU3F1 Protein-coding gene in the species Homo sapiens

POU domain, class 3, transcription factor 1 is a protein that in humans is encoded by the POU3F1 gene.

EMX2

Homeobox protein Emx2 is a protein that in humans is encoded by the EMX2 gene.

EGR3

Early growth response protein 3 is a protein in humans, encoded by the EGR3 gene.

OTX1

Homeobox protein OTX1 is a protein that in humans is encoded by the OTX1 gene.

POU2F3

POU domain, class 2, transcription factor 3 is a protein that in humans is encoded by the POU2F3 gene.

POU3F4 Protein-coding gene in the species Homo sapiens

POU domain, class 3, transcription factor 4 is a protein that in humans is encoded by the POU3F4 gene found on the X chromosome.

RIT2 Protein-coding gene in humans

GTP-binding protein Rit2 is a protein that in humans is encoded by the RIT2 gene.

EMX1 Protein-coding gene in the species Homo sapiens

Homeobox protein EMX1 is a protein that in humans is encoded by the EMX1 gene. The transcribed EMX1 gene is a member of the EMX family of transcription factors. The EMX1 gene, along with its family members, are expressed in the developing cerebrum. Emx1 plays a role in specification of positional identity, the proliferation of neural stem cells, differentiation of layer-specific neuronal phenotypes and commitment to a neuronal or glial cell fate.

POU4F3 Protein-coding gene in the species Homo sapiens

POU domain, class 4, transcription factor 3 is a protein that in humans is encoded by the POU4F3 gene. It's a member of BRN-3 group, also known as POU family class 4.

Neurogenin-2

Neurogenin-2 is a protein that in humans is encoded by the NEUROG2 gene.

References

  1. 1 2 3 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. Collum RG, Fisher PE, Datta M, Mellis S, Thiele C, Huebner K, Croce CM, Israel MA, Theil T, Moroy T (Sep 1992). "A novel POU homeodomain gene specifically expressed in cells of the developing mammalian nervous system". Nucleic Acids Research. 20 (18): 4919–25. doi:10.1093/nar/20.18.4919. PMC   334251 . PMID   1357630.
  5. 1 2 "Entrez Gene: POU4F1 POU domain, class 4, transcription factor 1".
  6. 1 2 Gerrero MR, McEvilly RJ, Turner E, Lin CR, O'Connell S, Jenne KJ, Hobbs MV, Rosenfeld MG (Nov 1993). "Brn-3.0: a POU-domain protein expressed in the sensory, immune, and endocrine systems that functions on elements distinct from known octamer motifs". Proceedings of the National Academy of Sciences of the United States of America. 90 (22): 10841–5. Bibcode:1993PNAS...9010841G. doi: 10.1073/pnas.90.22.10841 . PMC   47874 . PMID   8248179.
  7. He X, Treacy MN, Simmons DM, Ingraham HA, Swanson LW, Rosenfeld MG (Jul 1989). "Expression of a large family of POU-domain regulatory genes in mammalian brain development". Nature. 340 (6228): 35–41. Bibcode:1989Natur.340...35H. doi:10.1038/340035a0. PMID   2739723. S2CID   4275887.
  8. Xiang M, Zhou L, Macke JP, Yoshioka T, Hendry SH, Eddy RL, Shows TB, Nathans J (Jul 1995). "The Brn-3 family of POU-domain factors: primary structure, binding specificity, and expression in subsets of retinal ganglion cells and somatosensory neurons". The Journal of Neuroscience. 15 (7 Pt 1): 4762–85. doi:10.1523/JNEUROSCI.15-07-04762.1995. PMC   6577904 . PMID   7623109.
  9. Fedtsova NG, Turner EE (Nov 1995). "Brn-3.0 expression identifies early post-mitotic CNS neurons and sensory neural precursors". Mechanisms of Development. 53 (3): 291–304. doi: 10.1016/0925-4773(95)00435-1 . PMID   8645597.
  10. McEvilly RJ, Erkman L, Luo L, Sawchenko PE, Ryan AF, Rosenfeld MG (Dec 1996). "Requirement for Brn-3.0 in differentiation and survival of sensory and motor neurons". Nature. 384 (6609): 574–7. Bibcode:1996Natur.384..574M. doi:10.1038/384574a0. PMID   8955272. S2CID   4273651.
  11. Xiang M, Gan L, Zhou L, Klein WH, Nathans J (Oct 1996). "Targeted deletion of the mouse POU domain gene Brn-3a causes selective loss of neurons in the brainstem and trigeminal ganglion, uncoordinated limb movement, and impaired suckling". Proceedings of the National Academy of Sciences of the United States of America. 93 (21): 11950–5. Bibcode:1996PNAS...9311950X. doi: 10.1073/pnas.93.21.11950 . PMC   38164 . PMID   8876243.
  12. Eng SR, Gratwick K, Rhee JM, Fedtsova N, Gan L, Turner EE (Jan 2001). "Defects in sensory axon growth precede neuronal death in Brn3a-deficient mice". The Journal of Neuroscience. 21 (2): 541–9. doi:10.1523/JNEUROSCI.21-02-00541.2001. PMC   6763803 . PMID   11160433.
  13. 1 2 Eng SR, Lanier J, Fedtsova N, Turner EE (Aug 2004). "Coordinated regulation of gene expression by Brn3a in developing sensory ganglia". Development. 131 (16): 3859–70. doi: 10.1242/dev.01260 . PMID   15253936.
  14. Eng SR, Dykes IM, Lanier J, Fedtsova N, Turner EE (2007). "POU-domain factor Brn3a regulates both distinct and common programs of gene expression in the spinal and trigeminal sensory ganglia". Neural Development. 2 (1): 3. doi:10.1186/1749-8104-2-3. PMC   1796875 . PMID   17239249.
  15. Sun Y, Dykes IM, Liang X, Eng SR, Evans SM, Turner EE (Nov 2008). "A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs". Nature Neuroscience. 11 (11): 1283–93. doi:10.1038/nn.2209. PMC   2605652 . PMID   18849985.
  16. Dykes IM, Tempest L, Lee SI, Turner EE (Jul 2011). "Brn3a and Islet1 act epistatically to regulate the gene expression program of sensory differentiation". The Journal of Neuroscience. 31 (27): 9789–99. doi:10.1523/JNEUROSCI.0901-11.2011. PMC   3143040 . PMID   21734270.
  17. Trieu M, Ma A, Eng SR, Fedtsova N, Turner EE (Jan 2003). "Direct autoregulation and gene dosage compensation by POU-domain transcription factor Brn3a". Development. 130 (1): 111–21. doi: 10.1242/dev.00194 . PMID   12441296.
  18. Budhram-Mahadeo V, Parker M, Latchman DS (Feb 1998). "POU transcription factors Brn-3a and Brn-3b interact with the estrogen receptor and differentially regulate transcriptional activity via an estrogen response element". Molecular and Cellular Biology. 18 (2): 1029–41. doi:10.1128/mcb.18.2.1029. PMC   108815 . PMID   9448000.
  19. Calissano M, Latchman DS (Aug 2003). "Functional interaction between the small GTP-binding protein Rin and the N-terminal of Brn-3a transcription factor". Oncogene. 22 (35): 5408–14. doi: 10.1038/sj.onc.1206635 . PMID   12934100.
  20. Thomas GR, Latchman DS (2002). "The pro-oncoprotein EWS (Ewing's Sarcoma protein) interacts with the Brn-3a POU transcription factor and inhibits its ability to activate transcription". Cancer Biology & Therapy. 1 (4): 428–32. doi: 10.4161/cbt.1.4.23 . PMID   12432261.

Further reading

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