GeneID: 344


Common Name: TR4 Type: Gene
Chromosome: 3 (NC_000003.12) Locus: NM_003298.5 (NR2C2)
HUGO Symbol: NR2C2 Full Name: nuclear receptor subfamily 2 group C member 2
Exons: 15 Introns: 14

This gene encodes a protein that belongs to the nuclear hormone receptor family. Members of this family act as ligand-activated transcription factors and function in many biological processes such as development, cellular differentiation and homeostasis. The activated receptor/ligand complex is translocated to the nucleus where it binds to hormone response elements of target genes. Together with NR2C1 (TR2), it forms the core of the DRED (direct repeat erythroid-definitive) complex that binds to direct repeat (DR) elements (AGGTCA repeats) localised in the promoters of ε- and γ-globin genes, repressing their expression in definitive erythroid cells. Experimental evidence suggests that the TR2/TR4 complex is a stage-selective repressor of embryonic and fetal globin genes. However, forced expression of this complex in β-YAC transgenic mice and a humanized sickle cell disease (SCD) mouse model led to induction of the fetal γ-globin gene in adult erythroid cells and, in turn, to effective reversal of the disease phenotype. Modulating the activity of the TR2 and TR4 nuclear receptors could thus offer a promising therapeutic strategy for the treatment of SCD and β-thalassaemia.

Synonyms: TAK1


Sequence Viewer

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Publications / Origin

  1. Tanabe O, McPhee D, Kobayashi S, Shen Y, Brandt W, Jiang X, Campbell AD, Chen YT, Chang Cs, Yamamoto M, Tanimoto K, Engel JD, Embryonic and fetal beta-globin gene repression by the orphan nuclear receptors, TR2 and TR4., EMBO J., 26(9), 2295-306, 2007 PubMed
  2. Campbell AD, Cui S, Shi L, Urbonya R, Mathias A, Bradley K, Bonsu KO, Douglas RR, Halford B, Schmidt L, Harro D, Giacherio D, Tanimoto K, Tanabe O, Engel JD, Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes., Proc. Natl. Acad. Sci. U.S.A., 108(46), 18808-13, 2011 PubMed
Created on 2020-01-08 09:06:33, Last reviewed on (Show full history)

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