TCF3 (transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47))
2012-01-01 Jean-Loup Huret AffiliationGenetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Identity
HGNC
LOCATION
19p13.3
LOCUSID
ALIAS
AGM8,E2A,E47,ITF1,TCF-3,VDIR,bHLHb21,p75
FUSION GENES
DNA/RNA
Description
The E2A gene encodes two distinct basic helix-loop-helix transcription factors, E12 (ITF1) and E47 (TCF3) through alternative splicing.
Transcription
4,4 kb mRNA; coding sequence: 2,0 kb; alternate splicing --> E12 and E47, having different bHLH encoding exons (+ also E2-5).
Proteins
TCF3 (19p13.3) protein and domains.
Description
It forms homodimers and heterodimers with other basic helix-loop-helix transcription factors, such as ASCL1, MYOD1, TAL1, MYOG, NEUROG1, and TWIST1. It contains a transactivation domain (ADI) in N-term, a nuclear localization signal, activation domain II (ADII) (antiapoptotic), an ubiquitin ligase domain, a DNA binding motif, and a helix-loop-helix motif which mediates protein dimerisation in C-term.
Expression
Widely expressed.
Localisation
Nuclear.
Function
Ubiquitously expressed during development and in areas of rapid cell proliferation and differentiation. Role in cell growth, cell commitment, and differentiation. Role in epithelial mesenchymal transition. During epithelial mesenchymal transition, TGF-beta upregulates E2A proteins. E2A proteins are down regulated by the ubiquitin pathway (review in Slattery et al., 2008). Essential for normal B-cell hematopoiesis.
Homology
With other proteins with a helix-loop-helix dimerization domain signature, MYC type (MYC family, of which are MYC, LYL1, TAL1).
Implicated in
Entity name
Disease
pre B-ALL mainly; CD19+, CD10+, CD9+ (review in Hunger, 1996).
Prognosis
Controversial data; associated with poor prognostic features.
Cytogenetics
Two different forms:
- the balanced t(1;19);
- the unbalanced form, with 2 normal chromosomes 1, a der(19), and a normal chromosome19: --> partial trisomy for 1q23-1qter and monosomy for 19p13.3-pter;
additional anomalies: in half of the cases; they are various.
- the balanced t(1;19);
- the unbalanced form, with 2 normal chromosomes 1, a der(19), and a normal chromosome19: --> partial trisomy for 1q23-1qter and monosomy for 19p13.3-pter;
additional anomalies: in half of the cases; they are various.
Hybrid gene
5 TCF3 - 3 PBX1; breakpoints are clustered on both genes.
Fusion protein
N-term transcriptional activation domains from TCF3 fused to the Hox cooperative motif and homeodomain of C-term PBX1.
Oncogenesis
Potent transcriptional activator; pleiotropic transforming activity.
Disease
Pro-B acute lymphoblastic leukemia with expression of myeloid antigens (La Starza et al., 2005; Zhong et al., 2008).
Prognosis
Relatively good prognosis.
Cytogenetics
The t(12;19)(p13;p13) is cryptic.
Hybrid gene
5 TCF3 - 3 ZNF384
Entity name
t(13;19)(q14;p13)
Disease
Only one case to date, an adult patient with pre B-ALL; she achieved complete remission (Barber et al., 2007).
Hybrid gene
The translocation involves TCF3 and an unknown partner in 13q14.
Entity name
Disease
Childhood B-ALL (Raimondi et al., 1991; Hunger et al., 1992; Inaba et al., 1992; Devaraj et al., 1994; Mathew et al., 2001; Takahashi et al., 2001; Ribeiro et al., 2002; Yeung et al., 2006; Barber et al., 2007).
Prognosis
Poor prognosis is likely.
Hybrid gene
5 TCF3 - 3 HLF
Fusion protein
N-term transcriptional activation domains from TCF3 fused to the basic leucine zipper from HLF C-term.
Oncogenesis
TCF3/HLF homodimers bind to promoter/enhancer elements of downstream target genes.
Disease
Childhood pre-B cell acute lymphoblastic leukemia (Brambillasca et al., 1999).
Cytogenetics
This chromosome rearrangement is cryptic.
Hybrid gene
5 TCF3 - 3 TFPT
Fusion protein
Retains the transactivation domain of TCF3, but with a truncation in TFPT, due to the frequent occurrence of a stop codon.
Breakpoints
Note
Breakpoints: 1- in t(1;19): are located (and dispersed) in the intron 13, and remove the bHLH domain; 2- in t(17;19) type I: are so far located at a given nucleotide in intron 13; in t(17;19) type II: are located in intron 12.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17311319 | 2007 | Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B-cell precursor acute lymphoblastic leukemia. | Barber KE et al |
| 10086727 | 1999 | Identification of a novel molecular partner of the E2A gene in childhood leukemia. | Brambillasca F et al |
| 7518549 | 1994 | E2A/HLF fusion cDNAs and the use of RT-PCR for the detection of minimal residual disease in t(17;19)(q22;p13) acute lymphoblastic leukemia. | Devaraj PE et al |
| 8167343 | 1994 | Hairy cell leukemia is characterized by clonal chromosome abnormalities clustered to specific regions. | Haglund U et al |
| 1516826 | 1992 | Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia. | Hunger SP et al |
| 8608207 | 1996 | Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis. | Hunger SP et al |
| 1386162 | 1992 | Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia. | Inaba T et al |
| 9742120 | 1998 | The AD1 and AD2 transactivation domains of E2A are essential for the antiapoptotic activity of the chimeric oncoprotein E2A-HLF. | Inukai T et al |
| 15990865 | 2005 | CIZ gene rearrangements in acute leukemia: report of a diagnostic FISH assay and clinical features of nine patients. | La Starza R et al |
| 11237073 | 2001 | Multicolor spectral karyotyping identifies novel translocations in childhood acute lymphoblastic leukemia. | Mathew S et al |
| 2018838 | 1991 | New recurring chromosomal translocations in childhood acute lymphoblastic leukemia. | Raimondi SC et al |
| 11847518 | 2002 | Microsatellite instability and cytogenetic survey in myeloid leukemias. | Ribeiro EM et al |
| 17604208 | 2008 | E2A proteins: regulators of cell phenotype in normal physiology and disease. | Slattery C et al |
| 11417493 | 2001 | Expression of two types of E2A-HLF fusion proteins in YCUB-2, a novel cell line established from B-lineage leukemia with t(17;19). | Takahashi H et al |
| 16531271 | 2006 | Characterization of the t(17;19) translocation by gene-specific fluorescent in situ hybridization-based cytogenetics and detection of the E2A-HLF fusion transcript and protein in patients' cells. | Yeung J et al |
| 18185522 | 2008 | E2A-ZNF384 and NOL1-E2A fusion created by a cryptic t(12;19)(p13.3; p13.3) in acute leukemia. | Zhong CH et al |
Other Information
Locus ID:
NCBI: 6929
MIM: 147141
HGNC: 11633
Ensembl: ENSG00000071564
Variants:
dbSNP: 6929
ClinVar: 6929
TCGA: ENSG00000071564
COSMIC: TCF3
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37129918 | 2024 | Rare TCF3 variants associated with pediatric B cell acute lymphoblastic leukemia. | 0 |
| 38303515 | 2024 | Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis. | 1 |
| 37129918 | 2024 | Rare TCF3 variants associated with pediatric B cell acute lymphoblastic leukemia. | 0 |
| 38303515 | 2024 | Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis. | 1 |
| 36460773 | 2023 | FBXL2 promotes E47 protein instability to inhibit breast cancer stemness and paclitaxel resistance. | 4 |
| 36576946 | 2023 | Identification of TCF3 germline variants in pediatric B-cell acute lymphoblastic leukemia. | 4 |
| 37000263 | 2023 | Exportin XPO7 acts as an oncogenic factor in prostate cancer via upregulation of TCF3. | 0 |
| 37277074 | 2023 | TCF3 haploinsufficiency defined by immune, clinical, gene-dosage, and murine studies. | 1 |
| 37607071 | 2023 | Transcription factor 3 promotes migration and invasion potential and maintains cancer stemness by activating ID1 expression in esophageal squamous cell carcinoma. | 0 |
| 37704696 | 2023 | Molecular characterization of TCF3::PBX1 chromosomal breakpoints in acute lymphoblastic leukemia and their use for measurable residual disease assessment. | 2 |
| 37721971 | 2023 | Transcription Factor TCF3 Promotes Macrophage-Mediated Inflammation and MMP Secretion in Abdominal Aortic Aneurysm by Regulating miR-143-5p /CCL20. | 0 |
| 38047107 | 2023 | E47 as a novel glucocorticoid-dependent gene mediating lipid metabolism in patients with endogenous glucocorticoid excess. | 0 |
| 36460773 | 2023 | FBXL2 promotes E47 protein instability to inhibit breast cancer stemness and paclitaxel resistance. | 4 |
| 36576946 | 2023 | Identification of TCF3 germline variants in pediatric B-cell acute lymphoblastic leukemia. | 4 |
| 37000263 | 2023 | Exportin XPO7 acts as an oncogenic factor in prostate cancer via upregulation of TCF3. | 0 |
Citation
Jean-Loup Huret
TCF3 (transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47))
Atlas Genet Cytogenet Oncol Haematol. 2012-01-01
Online version: http://atlasgeneticsoncology.org/gene/50/tcf3-(transcription-factor-3-(e2a-immunoglobulin-enhancer-binding-factors-e12-e47))
Historical Card
1997-12-01 TCF3 (transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47)) by Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
