TCF3

Transcription factor 3

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1HLH, 2MH0, 2YPA, 2YPB, 3U5V

Identifiers

Symbols

TCF3 ; E2A; E47; ITF1; TCF-3; VDIR; bHLHb21

External IDs

OMIM: 147141 MGI: 98510 HomoloGene: 2408 GeneCards: TCF3 Gene

Gene ontology
Molecular function	• RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • DNA binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • transcription coactivator activity • protein binding • transcription factor binding • mitogen-activated protein kinase kinase kinase binding • enhancer binding • protein homodimerization activity • bHLH transcription factor binding • sequence-specific DNA binding • transcription regulatory region DNA binding • protein heterodimerization activity • repressing transcription factor binding • vitamin D response element binding • E-box binding
Cellular component	• nuclear nucleosome • nuclear chromatin • nucleus • nucleoplasm • transcription factor complex • cytoplasm • protein complex • RNA polymerase II transcription factor complex
Biological process	• negative regulation of transcription from RNA polymerase II promoter • natural killer cell differentiation • B cell lineage commitment • transcription, DNA-templated • regulation of transcription, DNA-templated • B cell differentiation • positive regulation of B cell proliferation • response to lipopolysaccharide • T cell differentiation in thymus • immunoglobulin V(D)J recombination • response to drug • muscle cell differentiation • histone H3 acetylation • histone H4 acetylation • positive regulation of neuron differentiation • positive regulation of cell cycle • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • cell development • Peyer's patch development • protein stabilization • positive regulation of sequence-specific DNA binding transcription factor activity • positive regulation of muscle cell differentiation • regulation of G1/S transition of mitotic cell cycle
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 19:
1.61 – 1.65 Mb

Chr 10:
80.41 – 80.43 Mb

PubMed search

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.^[1]^[2]^[3] TCF3 has been shown to directly enhance Hes1 (a well-known target of Notch signaling) expression.^[4]

Function

This gene encodes a member of the E protein (class I) family of helix-loop-helix transcription factors. 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 B and T lymphocyte development.^[1]

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.^[5] They initiate transcription by binding to regulatory E-box sequences on target genes. Additionally, development of the neocortex of the brain is controlled in part by a Wnt signaling pathway. This pathway is essential for proper neuronal differentiation and proliferation of neural precursor cells. However, Wnt must be suppressed until it is the appropriate time in development to initiate neuronal differentiation and proliferation of neural precursor cells.^[6] The TCF3 gene has been shown to play a role in suppressing Wnt for this purpose. Furthermore, TCF3 has been shown to represses β-catenin in this pathway as well.^[7] Undifferentiated neural precursor cells contain high expression of TCF3, but as those cells become more differentiated, the expression of TCF3 decreases. Therefore, lack of TCF3 increases neural precursor cell reprogramming and greater expression of TCF3 suppresses reprogramming of neural precursor cells.^[7] In a TCF3 knock out model in mice, the mesoderm forms, but the structures of the mesoderm, specifically structures of the CNS, are duplicated. Therefore, repressive functions of TCF3 are necessary for proper anterior-posterior axis development.^[8]

Clinical significance

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), childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384).^[1]

Interactions

TCF3 has been shown to interact with:

References

1 2 3 "Entrez Gene: TCF3".
↑ Henthorn P, McCarrick-Walmsley R, Kadesch T (Feb 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.
↑ Kamps MP, Murre C, Sun XH, Baltimore D (Feb 1990). "A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL". Cell 60 (4): 547–55. doi:10.1016/0092-8674(90)90658-2. PMID 1967983.
↑ E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment
↑ Quong MW, Romanow WJ, Murre C (2002). "E protein function in lymphocyte development". Annual Review of Immunology 20: 301–22. doi:10.1146/annurev.immunol.20.092501.162048. PMID 11861605.
↑ Kuwahara A, Sakai H, Xu Y, Itoh Y, Hirabayashi Y, Gotoh Y (2014). "Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development". PLOS ONE 9 (5): e94408. doi:10.1371/journal.pone.0094408. PMID 24832538.
1 2 Lluis F, Ombrato L, Pedone E, Pepe S, Merrill BJ, Cosma MP (Jul 2011). "T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications". Proceedings of the National Academy of Sciences of the United States of America 108 (29): 11912–7. doi:10.1073/pnas.1017402108. PMID 21730189.
↑ Merrill BJ, Pasolli HA, Polak L, Rendl M, García-García MJ, Anderson KV, Fuchs E (Jan 2004). "Tcf3: a transcriptional regulator of axis induction in the early embryo". Development 131 (2): 263–74. doi:10.1242/dev.00935. PMID 14668413.
1 2 3 Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P, Dumenil D, Strouboulis J, Romeo PH, Hoang T (Jan 2006). "ETO2 coordinates cellular proliferation and differentiation during erythropoiesis". The EMBO Journal 25 (2): 357–66. doi:10.1038/sj.emboj.7600934. PMC 1383517. PMID 16407974.
1 2 3 Bradney C, Hjelmeland M, Komatsu Y, Yoshida M, Yao TP, Zhuang Y (Jan 2003). "Regulation of E2A activities by histone acetyltransferases in B lymphocyte development". The Journal of Biological Chemistry 278 (4): 2370–6. doi:10.1074/jbc.M211464200. PMID 12435739.
↑ Maira SM, Wurtz JM, Wasylyk B (Nov 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): 5849–65. PMC 452333. PMID 8918463.
↑ Deed RW, Jasiok M, Norton JD (Apr 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): 8278–86. doi:10.1074/jbc.273.14.8278. PMID 9525934.
1 2 3 Langlands K, Yin X, Anand G, Prochownik EV (Aug 1997). "Differential interactions of Id proteins with basic-helix-loop-helix transcription factors". The Journal of Biological Chemistry 272 (32): 19785–93. doi:10.1074/jbc.272.32.19785. PMID 9242638.
↑ Johnson JD, Zhang W, Rudnick A, Rutter WJ, German MS (Jul 1997). "Transcriptional synergy between LIM-homeodomain proteins and basic helix-loop-helix proteins: the LIM2 domain determines specificity". Molecular and Cellular Biology 17 (7): 3488–96. doi:10.1128/mcb.17.7.3488. PMC 232202. PMID 9199284.
↑ Miyamoto 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): 2394–401. doi:10.1128/mcb.16.5.2394. PMC 231228. PMID 8628307.
↑ Neufeld B, Grosse-Wilde A, Hoffmeyer A, Jordan BW, Chen P, Dinev D, Ludwig S, Rapp UR (Jul 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): 20239–42. doi:10.1074/jbc.C901040199. PMID 10781029.
↑ Maleki SJ, Royer CA, Hurlburt BK (Jun 1997). "MyoD-E12 heterodimers and MyoD-MyoD homodimers are equally stable". Biochemistry 36 (22): 6762–7. doi:10.1021/bi970262m. PMID 9184158.
↑ Chakraborty T, Martin JF, Olson EN (Sep 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): 17498–501. PMID 1325437.
↑ Hsu HL, Wadman I, Baer R (Apr 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): 3181–5. doi:10.1073/pnas.91.8.3181. PMC 43539. PMID 8159721.
↑ El Ghouzzi V, Legeai-Mallet L, Aresta S, Benoist C, Munnich A, de Gunzburg J, Bonaventure J (Mar 2000). "Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location". Human Molecular Genetics 9 (5): 813–9. doi:10.1093/hmg/9.5.813. PMID 10749989.
↑ Huggins GS, Chin MT, Sibinga NE, Lee SL, Haber E, Lee ME (Oct 1999). "Characterization of the mUBC9-binding sites required for E2A protein degradation". The Journal of Biological Chemistry 274 (40): 28690–6. doi:10.1074/jbc.274.40.28690. PMID 10497239.

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1

(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2

(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)

(1.5) RF-X	RFX 1 2 3 4 5 6 ANK

(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR

subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX

subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ

subfamily 4	NUR NGFIB NOR1 NURR1

subfamily 5	LRH-1 SF1

subfamily 6	GCNF

subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2

(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX

(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4

(3.4) Heat shock factors	HSF 1 2 4

(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2

(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5

(4.2) STAT	STAT 1 2 3 4 5 6

(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63

(4.4) MADS box	Mef2 A B C D SRF

(4.6) TATA-binding proteins	TBP TBPL1

(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4

(4.9) Grainyhead	TFCP2

(4.10) Cold-shock domain	CSDA YBX1

(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1

(0.3) Pocket domain	Rb RBL1 RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3

(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

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TCF3

Function

Clinical significance

Interactions

References

Further reading