TCF4
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Transcription factor 4 (TCF-4) also known as immunoglobulin transcription factor 2 (ITF-2) is a protein that in humans is encoded by the TCF4 gene located on chromosome 18q21.1.[4]
Function
TCF4 proteins act as transcription factors which will bind to the immunoglobulin enhancer mu-E5/kappa-E2 motif. TCF4 activates transcription by binding to the E-box (5’-CANNTG-3’) found usually on SSTR2-INR, or somatostatin receptor 2 initiator element. TCF4 is primarily involved in neurological development of the fetus during pregnancy by initiating neural differentiation by binding to DNA. It is found in the central nervous system, somites, and gonadal ridge during early development. Later in development it will be found in the thyroid, thymus, and kidneys while in adulthood TCF4 it is found in lymphocytes, muscles, and gastrointestinal system.[5][6]
Clinical significance
Mutations in TCF4 cause Pitt-Hopkins Syndrome (PTHS). These mutations cause TCF4 proteins to not bind to DNA properly and control the differentiation of the nervous system. In most cases that have been studied, the mutations were de novo, meaning it was a new mutation not found in other family members of the patient. Common symptoms of Pitt-Hopkins Syndrome include a wide mouth, gastrointestinal problems, developmental delay of fine motor skills, speech and breathing problems, epilepsy, and other brain defects.[7][8]
References
- ↑ "Diseases that are genetically associated with TCF4 view/edit references on wikidata".
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- ↑ Henthorn P, McCarrick-Walmsley R, Kadesch T (Feb 1990). "Sequence of the cDNA encoding ITF-2, a positive-acting transcription factor". Nucleic Acids Research. 18 (3): 678. doi:10.1093/nar/18.3.678. PMC 333500
. PMID 2308860. - ↑ de Pontual L, Mathieu Y, Golzio C, Rio M, Malan V, Boddaert N, et al. (Apr 2009). "Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome". Human Mutation. 30 (4): 669–76. doi:10.1002/humu.20935. PMID 19235238.
- ↑ Pscherer A, Dörflinger U, Kirfel J, Gawlas K, Rüschoff J, Buettner R, Schüle R (Dec 1996). "The helix-loop-helix transcription factor SEF-2 regulates the activity of a novel initiator element in the promoter of the human somatostatin receptor II gene". The EMBO Journal. 15 (23): 6680–90. PMID 8978694.
- ↑ Amiel J, Rio M, de Pontual L, Redon R, Malan V, Boddaert N, et al. (May 2007). "Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction". American Journal of Human Genetics. 80 (5): 988–93. doi:10.1086/515582. PMID 17436254.
- ↑ Zweier C, Peippo MM, Hoyer J, Sousa S, Bottani A, Clayton-Smith J, et al. (May 2007). "Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome)". American Journal of Human Genetics. 80 (5): 994–1001. doi:10.1086/515583. PMC 1852727. PMID 17436255.
Further reading
- Herbst A, Helferich S, Behrens A, Göke B, Kolligs FT (Oct 2009). "The transcription factor ITF-2A induces cell cycle arrest via p21(Cip1)". Biochemical and Biophysical Research Communications. 387 (4): 736–40. doi:10.1016/j.bbrc.2009.07.102. PMID 19635457.
- Cisse B, Caton ML, Lehner M, Maeda T, Scheu S, Locksley R, Holmberg D, Zweier C, den Hollander NS, Kant SG, Holter W, Rauch A, Zhuang Y, Reizis B (Oct 2008). "Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development". Cell. 135 (1): 37–48. doi:10.1016/j.cell.2008.09.016. PMC 2631034. PMID 18854153.
- Bain G, Murre C (Apr 1998). "The role of E-proteins in B- and T-lymphocyte development". Seminars in Immunology. 10 (2): 143–53. doi:10.1006/smim.1998.0116. PMID 9618760.
- Yerges LM, Klei L, Cauley JA, Roeder K, Kammerer CM, Moffett SP, et al. (Dec 2009). "High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men". Journal of Bone and Mineral Research. 24 (12): 2039–49. doi:10.1359/jbmr.090524. PMC 2791518. PMID 19453261.
- Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P (Aug 2009). "Common polygenic variation contributes to risk of schizophrenia and bipolar disorder". Nature. 460 (7256): 748–52. doi:10.1038/nature08185. PMID 19571811.
- Kalscheuer VM, Feenstra I, Van Ravenswaaij-Arts CM, Smeets DF, Menzel C, Ullmann R, Musante L, Ropers HH (Aug 2008). "Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt-Hopkins syndrome". American Journal of Medical Genetics Part A. 146A (16): 2053–9. doi:10.1002/ajmg.a.32419. PMID 18627065.
- Herbst A, Bommer GT, Kriegl L, Jung A, Behrens A, Csanadi E, et al. (Aug 2009). "ITF-2 is disrupted via allelic loss of chromosome 18q21, and ITF-2B expression is lost at the adenoma-carcinoma transition". Gastroenterology. 137 (2): 639–48, 648.e1–9. doi:10.1053/j.gastro.2009.04.049. PMID 19394332.
- Nagasawa M, Schmidlin H, Hazekamp MG, Schotte R, Blom B (Sep 2008). "Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix-loop-helix factor E2-2 and the Ets factor Spi-B". European Journal of Immunology. 38 (9): 2389–400. doi:10.1002/eji.200838470. PMID 18792017.
- Rosenfeld JA, Leppig K, Ballif BC, Thiese H, Erdie-Lalena C, Bawle E, Sastry S, Spence JE, Bandholz A, Surti U, Zonana J, Keller K, Meschino W, Bejjani BA, Torchia BS, Shaffer LG (Nov 2009). "Genotype-phenotype analysis of TCF4 mutations causing Pitt-Hopkins syndrome shows increased seizure activity with missense mutations". Genetics in Medicine. 11 (11): 797–805. doi:10.1097/GIM.0b013e3181bd38a9. PMID 19938247.
- Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D, et al. (Aug 2009). "Common variants conferring risk of schizophrenia". Nature. 460 (7256): 744–7. doi:10.1038/nature08186. PMC 3077530. PMID 19571808.
External links
- TCF4 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
- FactorBook TCF4
This article incorporates text from the United States National Library of Medicine, which is in the public domain.