TCF4
Transcription factor 4 (TCF-4) also known as immunoglobulin transcription factor 2 (ITF-2) is a
chromosome 18q21.2.[5]
Function
TCF4 proteins act as
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, mature neurons, and gastrointestinal system.[6][7][8]
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. It has been suggested that TCF4 loss-of-function leads to decreased Wnt signaling and, consequently, a reduced neural progenitor proliferation.[9] 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.[10][11]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000196628 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000053477 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 2308860.
- S2CID 25375730.
- PMID 8978694.
- PMID 27050508.
- PMID 35501322.
- PMID 17436254.
- PMID 17436255.
Further reading
- Herbst A, Helferich S, Behrens A, Göke B, Kolligs FT (October 2009). "The transcription factor ITF-2A induces cell cycle arrest via p21(Cip1)". Biochemical and Biophysical Research Communications. 387 (4): 736–740. PMID 19635457.
- Cisse B, Caton ML, Lehner M, Maeda T, Scheu S, Locksley R, et al. (October 2008). "Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development". Cell. 135 (1): 37–48. PMID 18854153.
- Bain G, Murre C (April 1998). "The role of E-proteins in B- and T-lymphocyte development". Seminars in Immunology. 10 (2): 143–153. PMID 9618760.
- Yerges LM, Klei L, Cauley JA, Roeder K, Kammerer CM, Moffett SP, et al. (December 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): 2039–2049. PMID 19453261.
- Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P (August 2009). "Common polygenic variation contributes to risk of schizophrenia and bipolar disorder". Nature. 460 (7256): 748–752. PMID 19571811.
- Kalscheuer VM, Feenstra I, Van Ravenswaaij-Arts CM, Smeets DF, Menzel C, Ullmann R, et al. (August 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): 2053–2059. S2CID 205309738.
- Herbst A, Bommer GT, Kriegl L, Jung A, Behrens A, Csanadi E, et al. (August 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. PMID 19394332.
- Nagasawa M, Schmidlin H, Hazekamp MG, Schotte R, Blom B (September 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): 2389–2400. S2CID 205784742.
- Rosenfeld JA, Leppig K, Ballif BC, Thiese H, Erdie-Lalena C, Bawle E, et al. (November 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. PMID 19938247.
- Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D, et al. (August 2009). "Common variants conferring risk of schizophrenia". Nature. 460 (7256): 744–747. PMID 19571808.
External links
- TCF4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- FactorBook TCF4
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