“TCF4”的意思、由来-开放百科全书

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.^[2]^[3]

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.^[4]^[5]

References

1. ^{{cite journal | vauthors = Henthorn P, McCarrick-Walmsley R, Kadesch T | title = Sequence of the cDNA encoding ITF-2, a positive-acting transcription factor | journal = Nucleic Acids Research | volume = 18 | issue = 3 | pages = 678 | date = Feb 1990 | pmid = 2308860 | pmc = 333500 | doi = 10.1093/nar/18.3.678 | url = http://nar.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=2308860 }}
2. ^{{cite journal | vauthors = de Pontual L, Mathieu Y, Golzio C, Rio M, Malan V, Boddaert N, Soufflet C, Picard C, Durandy A, Dobbie A, Heron D, Isidor B, Motte J, Newburry-Ecob R, Pasquier L, Tardieu M, Viot G, Jaubert F, Munnich A, Colleaux L, Vekemans M, Etchevers H, Lyonnet S, Amiel J | display-authors = 6 | title = Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome | journal = Human Mutation | volume = 30 | issue = 4 | pages = 669–76 | date = Apr 2009 | pmid = 19235238 | doi = 10.1002/humu.20935 }}
3. ^{{cite journal | vauthors = Pscherer A, Dörflinger U, Kirfel J, Gawlas K, Rüschoff J, Buettner R, Schüle R | title = 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 | journal = The EMBO Journal | volume = 15 | issue = 23 | pages = 6680–90 | date = Dec 1996 | pmid = 8978694 | pmc=452492}}
4. ^{{cite journal | vauthors = Amiel J, Rio M, de Pontual L, Redon R, Malan V, Boddaert N, Plouin P, Carter NP, Lyonnet S, Munnich A, Colleaux L | display-authors = 6 | title = 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 | journal = American Journal of Human Genetics | volume = 80 | issue = 5 | pages = 988–93 | date = May 2007 | pmid = 17436254 | doi = 10.1086/515582 | pmc=1852736}}
5. ^{{cite journal | vauthors = Zweier C, Peippo MM, Hoyer J, Sousa S, Bottani A, Clayton-Smith J, Reardon W, Saraiva J, Cabral A, Gohring I, Devriendt K, de Ravel T, Bijlsma EK, Hennekam RC, Orrico A, Cohen M, Dreweke A, Reis A, Nurnberg P, Rauch A | display-authors = 6 | title = Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome) | journal = American Journal of Human Genetics | volume = 80 | issue = 5 | pages = 994–1001 | date = May 2007 | pmid = 17436255 | pmc = 1852727 | doi = 10.1086/515583 }}

Further reading

{{cite journal | vauthors = Herbst A, Helferich S, Behrens A, Göke B, Kolligs FT | title = The transcription factor ITF-2A induces cell cycle arrest via p21(Cip1) | journal = Biochemical and Biophysical Research Communications | volume = 387 | issue = 4 | pages = 736–40 | date = Oct 2009 | pmid = 19635457 | doi = 10.1016/j.bbrc.2009.07.102 }}

{{cite journal | vauthors = 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 | title = Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development | journal = Cell | volume = 135 | issue = 1 | pages = 37–48 | date = Oct 2008 | pmid = 18854153 | pmc = 2631034 | doi = 10.1016/j.cell.2008.09.016 }}

{{cite journal | vauthors = Bain G, Murre C | title = The role of E-proteins in B- and T-lymphocyte development | journal = Seminars in Immunology | volume = 10 | issue = 2 | pages = 143–53 | date = Apr 1998 | pmid = 9618760 | doi = 10.1006/smim.1998.0116 }}

{{cite journal | vauthors = Yerges LM, Klei L, Cauley JA, Roeder K, Kammerer CM, Moffett SP, Ensrud KE, Nestlerode CS, Marshall LM, Hoffman AR, Lewis C, Lang TF, Barrett-Connor E, Ferrell RE, Orwoll ES, Zmuda JM | display-authors = 6 | title = High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men | journal = Journal of Bone and Mineral Research | volume = 24 | issue = 12 | pages = 2039–49 | date = Dec 2009 | pmid = 19453261 | pmc = 2791518 | doi = 10.1359/jbmr.090524 }}

{{cite journal | vauthors = Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P | title = Common polygenic variation contributes to risk of schizophrenia and bipolar disorder | journal = Nature | volume = 460 | issue = 7256 | pages = 748–52 | date = Aug 2009 | pmid = 19571811 | doi = 10.1038/nature08185 | pmc = 3912837 }}

{{cite journal | vauthors = Kalscheuer VM, Feenstra I, Van Ravenswaaij-Arts CM, Smeets DF, Menzel C, Ullmann R, Musante L, Ropers HH | title = Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt-Hopkins syndrome | journal = American Journal of Medical Genetics Part A | volume = 146A | issue = 16 | pages = 2053–9 | date = Aug 2008 | pmid = 18627065 | doi = 10.1002/ajmg.a.32419 }}

{{cite journal | vauthors = Herbst A, Bommer GT, Kriegl L, Jung A, Behrens A, Csanadi E, Gerhard M, Bolz C, Riesenberg R, Zimmermann W, Dietmaier W, Wolf I, Brabletz T, Göke B, Kolligs FT | display-authors = 6 | title = ITF-2 is disrupted via allelic loss of chromosome 18q21, and ITF-2B expression is lost at the adenoma-carcinoma transition | journal = Gastroenterology | volume = 137 | issue = 2 | pages = 639–48, 648.e1-9 | date = Aug 2009 | pmid = 19394332 | doi = 10.1053/j.gastro.2009.04.049 }}

{{cite journal | vauthors = Nagasawa M, Schmidlin H, Hazekamp MG, Schotte R, Blom B | title = 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 | journal = European Journal of Immunology | volume = 38 | issue = 9 | pages = 2389–400 | date = Sep 2008 | pmid = 18792017 | doi = 10.1002/eji.200838470 }}

{{cite journal | vauthors = 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 | title = Genotype-phenotype analysis of TCF4 mutations causing Pitt-Hopkins syndrome shows increased seizure activity with missense mutations | journal = Genetics in Medicine | volume = 11 | issue = 11 | pages = 797–805 | date = Nov 2009 | pmid = 19938247 | doi = 10.1097/GIM.0b013e3181bd38a9 }}

{{cite journal | vauthors = Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D, Werge T, Pietiläinen OP, Mors O, Mortensen PB, Sigurdsson E, Gustafsson O, Nyegaard M, Tuulio-Henriksson A, Ingason A, Hansen T, Suvisaari J, Lonnqvist J, Paunio T, Børglum AD, Hartmann A, Fink-Jensen A, Nordentoft M, Hougaard D, Norgaard-Pedersen B, Böttcher Y, Olesen J, Breuer R, Möller HJ, Giegling I, Rasmussen HB, Timm S, Mattheisen M, Bitter I, Réthelyi JM, Magnusdottir BB, Sigmundsson T, Olason P, Masson G, Gulcher JR, Haraldsson M, Fossdal R, Thorgeirsson TE, Thorsteinsdottir U, Ruggeri M, Tosato S, Franke B, Strengman E, Kiemeney LA, Melle I, Djurovic S, Abramova L, Kaleda V, Sanjuan J, de Frutos R, Bramon E, Vassos E, Fraser G, Ettinger U, Picchioni M, Walker N, Toulopoulou T, Need AC, Ge D, Yoon JL, Shianna KV, Freimer NB, Cantor RM, Murray R, Kong A, Golimbet V, Carracedo A, Arango C, Costas J, Jönsson EG, Terenius L, Agartz I, Petursson H, Nöthen MM, Rietschel M, Matthews PM, Muglia P, Peltonen L, St Clair D, Goldstein DB, Stefansson K, Collier DA | display-authors = 6 | title = Common variants conferring risk of schizophrenia | journal = Nature | volume = 460 | issue = 7256 | pages = 744–7 | date = Aug 2009 | pmid = 19571808 | pmc = 3077530 | doi = 10.1038/nature08186 }}

Function

Clinical significance

References

Further reading

External links