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Transcription factor 3 (E2A immunoglobulin enhancer-binding factors E12/E47), also known as TCF3, is a protein that in humans is encoded by the TCF3 gene.cite-ref-entrez-6929-5-0[5]cite-ref-pmid2308859-6-0[6]cite-ref-pmid1967983-7-0[7] TCF3 has been shown to directly enhance Hes1 (a well-known target of Notch signaling) expression.cite-ref-8[8]

• Function

• Clinical significance

• Interactions

• References

• Further reading

This gene encodes a member of the E protein (class I) family of helix-loop-helix transcription factors. The 9aaTAD transactivation domains of E proteins and MLL are very similar and both bind to the KIX domain of general transcriptional mediator CBP.cite-ref-9[9]cite-ref-10[10] E proteins activate transcription by binding to regulatory E-box sequences on target genes as heterodimers or homodimers, and are inhibited by heterodimerization with inhibitor of DNA-binding (class IV) helix-loop-helix proteins. E proteins play a critical role in lymphopoiesis, and the encoded protein is required for the B and T lymphocyte development.cite-ref-entrez-6929-5-1[5]

This gene regulates many developmental patterning processes such as lymphocyte and central nervous system (CNS) development. E proteins are involved in the development of lymphocytes.cite-ref-11[11] They initiate transcription by binding to regulatory E-box sequences on target genes.

Deletion of this gene or diminished activity of the encoded protein may play a role in lymphoid malignancies. This gene is also involved in several chromosomal translocations that are associated with lymphoid malignancies including pre-B-cell acute lymphoblastic leukemia (t(1;19), with PBX1 and t(17;19), with HLF),cite-ref-12[12] childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384).cite-ref-entrez-6929-5-2[5]

TCF3 has been shown to interact with:

• CBFA2T3,cite-ref-pmid16407974-13-0[13]

• CREBBP,cite-ref-pmid12435739-14-0[14]

• ELK3,cite-ref-pmid8918463-15-0[15]

• EP300,cite-ref-pmid12435739-14-1[14]

• ID3,cite-ref-pmid9525934-16-0[16]cite-ref-pmid9242638-17-0[17]

• LDB1,cite-ref-pmid16407974-13-1[13]

• LMX1A,cite-ref-pmid9199284-18-0[18]

• LYL1,cite-ref-pmid8628307-19-0[19]

• MAPKAPK3,cite-ref-pmid10781029-20-0[20]

• MyoD,cite-ref-pmid9242638-17-1[17]cite-ref-pmid9184158-21-0[21]

• Myogenin,cite-ref-pmid9242638-17-2[17]cite-ref-pmid1325437-22-0[22]

• PCAF,cite-ref-pmid12435739-14-2[14]

• TAL1cite-ref-pmid16407974-13-2[13]cite-ref-pmid8159721-23-0[23]

• TWIST1,cite-ref-pmid10749989-24-0[24] and

• UBE2I.cite-ref-pmid10497239-25-0[25]

cite-note-refgrch38ensembl-11. GRCh38: Ensembl release 89: ENSG00000071564 – Ensembl, May 2017

cite-note-refgrcm38ensembl-22. GRCm38: Ensembl release 89: ENSMUSG00000020167 – Ensembl, May 2017

cite-note-33. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

cite-note-44. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

cite-note-entrez-6929-55. ↑ "Entrez Gene: TCF3".

cite-note-pmid2308859-66. ↑ citerefhenthornmccarrick-walmsleykadesch1990Henthorn P, McCarrick-Walmsley R, Kadesch T (February 1990). "Sequence of the cDNA encoding ITF-1, a positive-acting transcription factor". Nucleic Acids Research. 18 (3): 677. doi:10.1093/nar/18.3.677. PMC 333499. PMID 2308859.

cite-note-pmid1967983-77. ↑ citerefkampsmurresunbaltimore1990Kamps MP, Murre C, Sun XH, Baltimore D (February 1990). "A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL". Cell. 60 (4): 547–555. doi:10.1016/0092-8674(90)90658-2. PMID 1967983. S2CID 39661371.

cite-note-88. ↑ E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment

cite-note-99. ↑ citerefpiskacekgregornemethovagrabner2007Piskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M (June 2007). "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics. 89 (6): 756–768. doi:10.1016/j.ygeno.2007.02.003. PMID 17467953.

cite-note-1010. ↑ citerefpiskacekvaskuhajekknight2015Piskacek M, Vasku A, Hajek R, Knight A (March 2015). "Shared structural features of the 9aaTAD family in complex with CBP". Molecular BioSystems. 11 (3): 844–851. doi:10.1039/c4mb00672k. PMID 25564305.

cite-note-1111. ↑ citerefquongromanowmurre2002Quong MW, Romanow WJ, Murre C (2002). "E protein function in lymphocyte development". Annual Review of Immunology. 20: 301–322. doi:10.1146/annurev.immunol.20.092501.162048. PMID 11861605.

cite-note-1212. ↑ citerefherblotaplanhoang2002Herblot S, Aplan PD, Hoang T (February 2002). "Gradient of E2A activity in B-cell development". Molecular and Cellular Biology. 22 (3): 886–900. doi:10.1128/MCB.22.3.886-900.2002. PMC 133542. PMID 11784864.

cite-note-pmid16407974-1313. ↑ citerefgoardonlambertrodrigueznissaire2006Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P, et al. (January 2006). "ETO2 coordinates cellular proliferation and differentiation during erythropoiesis". The EMBO Journal. 25 (2): 357–366. doi:10.1038/sj.emboj.7600934. PMC 1383517. PMID 16407974.

cite-note-pmid12435739-1414. ↑ citerefbradneyhjelmelandkomatsuyoshida2003Bradney C, Hjelmeland M, Komatsu Y, Yoshida M, Yao TP, Zhuang Y (January 2003). "Regulation of E2A activities by histone acetyltransferases in B lymphocyte development". The Journal of Biological Chemistry. 278 (4): 2370–2376. doi:10.1074/jbc.M211464200. PMID 12435739.

cite-note-pmid8918463-1515. ↑ citerefmairawurtzwasylyk1996Maira SM, Wurtz JM, Wasylyk B (November 1996). "Net (ERP/SAP2) one of the Ras-inducible TCFs, has a novel inhibitory domain with resemblance to the helix-loop-helix motif". The EMBO Journal. 15 (21): 5849–5865. doi:10.1002/j.1460-2075.1996.tb00972.x. PMC 452333. PMID 8918463.

cite-note-pmid9525934-1616. ↑ citerefdeedjasioknorton1998Deed RW, Jasiok M, Norton JD (April 1998). "Lymphoid-specific expression of the Id3 gene in hematopoietic cells. Selective antagonism of E2A basic helix-loop-helix protein associated with Id3-induced differentiation of erythroleukemia cells". The Journal of Biological Chemistry. 273 (14): 8278–8286. doi:10.1074/jbc.273.14.8278. PMID 9525934.

cite-note-pmid9242638-1717. ↑ citereflanglandsyinanandprochownik1997Langlands K, Yin X, Anand G, Prochownik EV (August 1997). "Differential interactions of Id proteins with basic-helix-loop-helix transcription factors". The Journal of Biological Chemistry. 272 (32): 19785–19793. doi:10.1074/jbc.272.32.19785. PMID 9242638.

cite-note-pmid9199284-1818. ↑ citerefjohnsonzhangrudnickrutter1997Johnson JD, Zhang W, Rudnick A, Rutter WJ, German MS (July 1997). "Transcriptional synergy between LIM-homeodomain proteins and basic helix-loop-helix proteins: the LIM2 domain determines specificity". Molecular and Cellular Biology. 17 (7): 3488–3496. doi:10.1128/mcb.17.7.3488. PMC 232202. PMID 9199284.

cite-note-pmid8628307-1919. ↑ citerefmiyamotocuinaumovskicleary1996Miyamoto A, Cui X, Naumovski L, Cleary ML (May 1996). "Helix-loop-helix proteins LYL1 and E2a form heterodimeric complexes with distinctive DNA-binding properties in hematolymphoid cells". Molecular and Cellular Biology. 16 (5): 2394–2401. doi:10.1128/mcb.16.5.2394. PMC 231228. PMID 8628307.

cite-note-pmid10781029-2020. ↑ citerefneufeldgrosse-wildehoffmeyerjordan2000Neufeld B, Grosse-Wilde A, Hoffmeyer A, Jordan BW, Chen P, Dinev D, et al. (July 2000). "Serine/Threonine kinases 3pK and MAPK-activated protein kinase 2 interact with the basic helix-loop-helix transcription factor E47 and repress its transcriptional activity". The Journal of Biological Chemistry. 275 (27): 20239–20242. doi:10.1074/jbc.C901040199. PMID 10781029.

cite-note-pmid9184158-2121. ↑ citerefmalekiroyerhurlburt1997Maleki SJ, Royer CA, Hurlburt BK (June 1997). "MyoD-E12 heterodimers and MyoD-MyoD homodimers are equally stable". Biochemistry. 36 (22): 6762–6767. doi:10.1021/bi970262m. PMID 9184158.

cite-note-pmid1325437-2222. ↑ citerefchakrabortymartinolson1992Chakraborty T, Martin JF, Olson EN (September 1992). "Analysis of the oligomerization of myogenin and E2A products in vivo using a two-hybrid assay system". The Journal of Biological Chemistry. 267 (25): 17498–17501. doi:10.1016/S0021-9258(19)37069-3. PMID 1325437.

cite-note-pmid8159721-2323. ↑ citerefhsuwadmanbaer1994Hsu HL, Wadman I, Baer R (April 1994). "Formation of in vivo complexes between the TAL1 and E2A polypeptides of leukemic T cells". Proceedings of the National Academy of Sciences of the United States of America. 91 (8): 3181–3185. Bibcode:1994PNAS...91.3181H. doi:10.1073/pnas.91.8.3181. PMC 43539. PMID 8159721.

cite-note-pmid10749989-2424. ↑ citerefel-ghouzzilegeai-malletarestabenoist2000El Ghouzzi V, Legeai-Mallet L, Aresta S, Benoist C, Munnich A, de Gunzburg J, et al. (March 2000). "Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location". Human Molecular Genetics. 9 (5): 813–819. doi:10.1093/hmg/9.5.813. PMID 10749989.

cite-note-pmid10497239-2525. ↑ citerefhugginschinsibingalee1999Huggins GS, Chin MT, Sibinga NE, Lee SL, Haber E, Lee ME (October 1999). "Characterization of the mUBC9-binding sites required for E2A protein degradation". The Journal of Biological Chemistry. 274 (40): 28690–28696. doi:10.1074/jbc.274.40.28690. PMID 10497239.

• citereflebrun2003LeBrun DP (May 2003). "E2A basic helix-loop-helix transcription factors in human leukemia". Frontiers in Bioscience. 8 (1–3): s206 – s222. doi:10.2741/1030. PMID 12700034.