TLX

Nuclear receptor subfamily 2, group E, member 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4XAJ​
Identifiers
Symbols	NR2E1 ; TLL; TLX; XTLL
External IDs	OMIM: 603849 MGI: 1100526 HomoloGene: 37750 IUPHAR: 615 GeneCards: NR2E1 Gene
Gene ontology Molecular function • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • steroid hormone receptor activity • zinc ion binding • histone deacetylase binding • sequence-specific DNA binding Cellular component • nucleoplasm Biological process • negative regulation of transcription from RNA polymerase II promoter • behavioral fear response • aggressive behavior • transcription initiation from RNA polymerase II promoter • nervous system development • visual perception • gene expression • dentate gyrus development • amygdala development • olfactory bulb development • layer formation in cerebral cortex • forebrain generation of neurons • cerebral cortex neuron differentiation • anterior commissure morphogenesis • extracellular matrix organization • somatic stem cell maintenance • social behavior • negative regulation of apoptotic process • steroid hormone mediated signaling pathway • cell fate commitment • negative regulation of neuron differentiation • positive regulation of angiogenesis • positive regulation of cell cycle • positive regulation of transcription from RNA polymerase II promoter • negative regulation of astrocyte differentiation • regulation of dendrite morphogenesis • retina development in camera-type eye • regulation of timing of neuron differentiation • long-term synaptic potentiation • regulation of cell migration involved in sprouting angiogenesis • negative regulation of neural precursor cell proliferation • positive regulation of neural precursor cell proliferation • positive regulation of stem cell proliferation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7101	21907
Ensembl	ENSG00000112333	ENSMUSG00000019803
UniProt	Q9Y466	Q64104
RefSeq (mRNA)	NM_001286102	NM_152229
RefSeq (protein)	NP_001273031	NP_689415
Location (UCSC)	Chr 6: 108.17 – 108.19 Mb	Chr 10: 42.56 – 42.58 Mb
PubMed search

Nuclear receptor TLX (homologue of the Drosophila tailless gene) also known as NR2E1 (Nuclear receptor subfamily 2 group E member 1) is a protein that in humans is encoded by the NR2E1 gene.^[1] TLX is a member of the nuclear receptor family of intracellular transcription factors.

Function

TLX regulates the expression of another nuclear receptor, RAR.^[2]

TLX also is essential for normal brain-eye coordination and appears to play a role in control of aggressive behavior.^[3]

Adult neural stem cells are nuclear receptor TLX-positive and TLX expression in these cells is crucial in maintaining their undifferentiated state.^[4] Furthermore TLX regulates adult neural stem cell proliferation. Removal of TLX from the adult mouse brain resulted in a reduction of stem cell proliferation and spatial learning.^[5]

Tlx-positive cells of the subventricular zone of adult mouse brain are self-renewing stem cells. Mutation of the Tlx gene in adult mouse brain leads to complete loss of neurogenesis in the subventricular zone. Tlx is also required for transition from radial glial cells to astrocyte-like neural stem cells.^[6]

References

1. Jackson A, Panayiotidis P, Foroni L (May 1998). "The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21". Genomics 50 (1): 34–43. doi:10.1006/geno.1998.5270. PMID 9628820.
2. Kobayashi M, Yu RT, Yasuda K, Umesono K (Dec 2000). "Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX". Molecular and Cellular Biology 20 (23): 8731–9. doi:10.1128/MCB.20.23.8731-8739.2000. PMC 86495. PMID 11073974.
3. Abrahams BS, Kwok MC, Trinh E, Budaghzadeh S, Hossain SM, Simpson EM (Jul 2005). "Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1". The Journal of Neuroscience 25 (27): 6263–70. doi:10.1523/JNEUROSCI.4757-04.2005. PMID 16000615.
4. Shi Y, Chichung Lie D, Taupin P, Nakashima K, Ray J, Yu RT, Gage FH, Evans RM (Jan 2004). "Expression and function of orphan nuclear receptor TLX in adult neural stem cells". Nature 427 (6969): 78–83. doi:10.1038/nature02211. PMID 14702088.
5. Zhang CL, Zou Y, He W, Gage FH, Evans RM (Feb 2008). "A role for adult TLX-positive neural stem cells in learning and behaviour". Nature 451 (7181): 1004–7. doi:10.1038/nature06562. PMID 18235445.
6. Liu HK, Belz T, Bock D, Takacs A, Wu H, Lichter P, Chai M, Schütz G (Sep 2008). "The nuclear receptor tailless is required for neurogenesis in the adult subventricular zone". Genes & Development 22 (18): 2473–8. doi:10.1101/gad.479308. PMC 2546695. PMID 18794344.

Further reading

• Yu RT, McKeown M, Evans RM, Umesono K (Aug 1994). "Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx". Nature 370 (6488): 375–9. doi:10.1038/370375a0. PMID 8047143.
• Kobayashi M, Yu RT, Yasuda K, Umesono K (Dec 2000). "Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX". Molecular and Cellular Biology 20 (23): 8731–9. doi:10.1128/MCB.20.23.8731-8739.2000. PMC 86495. PMID 11073974.
• Abrahams BS, Mak GM, Berry ML, Palmquist DL, Saionz JR, Tay A, Tan YH, Brenner S, Simpson EM, Venkatesh B (Jul 2002). "Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci". Genomics 80 (1): 45–53. doi:10.1006/geno.2002.6795. PMID 12079282.
• Abrahams BS, Kwok MC, Trinh E, Budaghzadeh S, Hossain SM, Simpson EM (Jul 2005). "Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1". The Journal of Neuroscience 25 (27): 6263–70. doi:10.1523/JNEUROSCI.4757-04.2005. PMID 16000615.
• Kumar RA, Leach S, Bonaguro R, Chen J, Yokom DW, Abrahams BS, Seaver L, Schwartz CE, Dobyns W, Brooks-Wilson A, Simpson EM (Aug 2007). "Mutation and evolutionary analyses identify NR2E1-candidate-regulatory mutations in humans with severe cortical malformations". Genes, Brain, and Behavior 6 (6): 503–16. doi:10.1111/j.1601-183X.2006.00277.x. PMC 2040186. PMID 17054721.
• Kumar RA, Everman DB, Morgan CT, Slavotinek A, Schwartz CE, Simpson EM (2007). "Absence of mutations in NR2E1 and SNX3 in five patients with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and related phenotypes". BMC Medical Genetics 8: 48. doi:10.1186/1471-2350-8-48. PMC 1950490. PMID 17655765.
• Sun G, Yu RT, Evans RM, Shi Y (Sep 2007). "Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation". Proceedings of the National Academy of Sciences of the United States of America 104 (39): 15282–7. doi:10.1073/pnas.0704089104. PMC 2000559. PMID 17873065.

External links

• NR2E1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)