TLX

Nuclear receptor subfamily 2, group E, member 1
Identifiers
Symbols	NR2E1; TLL; TLX; XTLL
External IDs	OMIM: 603849 MGI: 1100526 HomoloGene: 37750 IUPHAR: NR2E1 GeneCards: NR2E1 Gene
Gene Ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription • sequence-specific DNA binding transcription factor activity • steroid hormone receptor activity • zinc ion binding • sequence-specific DNA binding • metal ion binding Cellular component • nucleus • nucleoplasm Biological process • behavioral fear response • aggressive behavior • multicellular organismal development • nervous system development • brain development • visual perception • behavior • positive regulation of cell proliferation • glial cell migration • 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 • cerebral cortex development • extracellular matrix organization • regulation of transcription from RNA polymerase II promoter by nuclear hormone receptor • somatic stem cell maintenance • social behavior • negative regulation of apoptosis • steroid hormone mediated signaling pathway • cell fate commitment • negative regulation of neuron differentiation • positive regulation of angiogenesis • positive regulation of cell cycle • negative regulation of astrocyte differentiation • regulation of dendrite morphogenesis • regulation of cellular component organization • 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 Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7101	21907
Ensembl	ENSG00000112333	ENSMUSG00000019803
UniProt	Q9Y466	Q3UXE8
RefSeq (mRNA)	NM_003269.3	NM_152229.2
RefSeq (protein)	NP_003260.1	NP_689415.1
Location (UCSC)	Chr 6: 108.49 – 108.51 Mb	Chr 10: 42.28 – 42.3 Mb
PubMed search	[1]	[2]

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 (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 (2000). "Cell-Type-Specific Regulation of the Retinoic Acid Receptor Mediated by the Orphan Nuclear Receptor TLX". Mol. Cell. Biol. 20 (23): 8731–9. doi:10.1128/MCB.20.23.8731-8739.2000. PMC 86495. PMID 11073974. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86495. 
3. ^ Abrahams BS, Kwok MC, Trinh E, Budaghzadeh S, Hossain SM, Simpson EM (2005). "Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1". J. Neurosci. 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 (January 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 (February 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 (September 2008). "The nuclear receptor tailless is required for neurogenesis in the adult subventricular zone". Genes Dev. 22 (18): 2473–8. doi:10.1101/gad.479308. PMC 2546695. PMID 18794344. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2546695. 

Further reading

• Yu RT, McKeown M, Evans RM, Umesono K (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 (2000). "Cell-Type-Specific Regulation of the Retinoic Acid Receptor Mediated by the Orphan Nuclear Receptor TLX". Mol. Cell. Biol. 20 (23): 8731–9. doi:10.1128/MCB.20.23.8731-8739.2000. PMC 86495. PMID 11073974. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86495. 
• Abrahams BS, Mak GM, Berry ML, et al. (2003). "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. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Mungall AJ, Palmer SA, Sims SK, et al. (2003). "The DNA sequence and analysis of human chromosome 6". Nature 425 (6960): 805–11. doi:10.1038/nature02055. PMID 14574404. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Abrahams BS, Kwok MC, Trinh E, et al. (2006). "Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1". J. Neurosci. 25 (27): 6263–70. doi:10.1523/JNEUROSCI.4757-04.2005. PMID 16000615. 
• Kumar RA, Leach S, Bonaguro R, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2040186. 
• Kumar RA, Everman DB, Morgan CT, et al. (2007). "Absence of mutations in NR2E1 and SNX3 in five patients with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and related phenotypes". BMC Med. Genet. 8: 48. doi:10.1186/1471-2350-8-48. PMC 1950490. PMID 17655765. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1950490. 
• Sun G, Yu RT, Evans RM, Shi Y (2007). "Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation". Proc. Natl. Acad. Sci. U.S.A. 104 (39): 15282–7. doi:10.1073/pnas.0704089104. PMC 2000559. PMID 17873065. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2000559. 

External links

• MeSH NR2E1+protein,+human