Biology:TCF4

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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 18q21.2.[1]

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, mature neurons, and gastrointestinal system.[2][3][4]


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.[5] 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.[6][7]

References

  1. ↑ "Sequence of the cDNA encoding ITF-2, a positive-acting transcription factor". Nucleic Acids Research 18 (3): 678. February 1990. doi:10.1093/nar/18.3.678. PMID 2308860. 
  2. ↑ "Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome". Human Mutation 30 (4): 669–676. April 2009. doi:10.1002/humu.20935. PMID 19235238. 
  3. ↑ "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): 6680–6690. December 1996. doi:10.1002/j.1460-2075.1996.tb01058.x. PMID 8978694. 
  4. ↑ "Type I bHLH Proteins Daughterless and Tcf4 Restrict Neurite Branching and Synapse Formation by Repressing Neurexin in Postmitotic Neurons". Cell Reports 15 (2): 386–397. April 2016. doi:10.1016/j.celrep.2016.03.034. PMID 27050508. 
  5. ↑ "Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content". Nature Communications 13 (1): 2387. May 2022. doi:10.1038/s41467-022-29942-w. PMID 35501322. 
  6. ↑ "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): 988–993. May 2007. doi:10.1086/515582. PMID 17436254. 
  7. ↑ "Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome)". American Journal of Human Genetics 80 (5): 994–1001. May 2007. doi:10.1086/515583. PMID 17436255. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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