TFEC, a Basic Helix-loop-helix Protein, Forms Heterodimers with TFE3 and Inhibits TFE3-dependent Transcription Activation

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1993 Aug 1

PMID 8336698

Citations 45

Authors

G Q Zhao

Q Zhao

X Zhou

M G Mattei

B de Crombrugghe

Affiliations

Soon will be listed here.

Abstract

We have identified a new basic helix-loop-helix (BHLH) DNA-binding protein, designated TFEC, which is closely related to TFE3 and TFEB. The basic domain of TFEC is identical to the basic DNA-binding domain of TFE3 and TFEB, whereas the helix-loop-helix motif of TFEC shows 88 and 85% identity with the same domains in TFE3 and TFEB, respectively. Like the other two proteins, TFEC contains a leucine zipper motif, which has a lower degree of sequence identity with homologous domains in TFE3 and TFEB than does the BHLH segment. Little sequence identity exists outside these motifs. Unlike the two other proteins, TFEC does not contain an acidic domain, which for TFE3 mediates the ability to activate transcription. Like the in vitro translation product of TFE3, the in vitro-translated TFEC binds to the mu E3 DNA sequence of the immunoglobulin heavy-chain gene enhancer. In addition, the product of cotranslation of TFEC RNA and TFE3 RNA forms a heteromeric protein-DNA complex with mu E3 DNA. In contrast to TFE3, TFEC is unable to transactivate a reporter gene linked to a promoter containing tandem copies of the immunoglobulin mu E3 enhancer motif. Cotransfection of TFEC DNA and TFE3 DNA strongly inhibits the transactivation caused by TFE3. TFEC RNA is found in many tissues of adult rats, but the relative concentrations of TFEC and TFE3 RNAs vary considerably in these different tissues. No TFEC RNA was detectable in several cell lines, including fibroblasts, myoblasts, chondrosarcoma cells, and myeloma cells, indicating that TFEC is not ubiquitously expressed.

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References

Villares R, Cabrera C . The achaete-scute gene complex of D. melanogaster: conserved domains in a subset of genes required for neurogenesis and their homology to myc. Cell. 1987; 50(3):415-24. DOI: 10.1016/0092-8674(87)90495-8. View

Seed B, Aruffo A . Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc Natl Acad Sci U S A. 1987; 84(10):3365-9. PMC: 304871. DOI: 10.1073/pnas.84.10.3365. View

Davis R, Weintraub H, Lassar A . Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987; 51(6):987-1000. DOI: 10.1016/0092-8674(87)90585-x. View

Thisse B, Stoetzel C, Perrin-Schmitt F . Sequence of the twist gene and nuclear localization of its protein in endomesodermal cells of early Drosophila embryos. EMBO J. 1988; 7(7):2175-83. PMC: 454534. DOI: 10.1002/j.1460-2075.1988.tb03056.x. View

Caudy M, Vassin H, Brand M, Tuma R, Jan L, Jan Y . daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex. Cell. 1988; 55(6):1061-7. DOI: 10.1016/0092-8674(88)90250-4. View

Wright W, Sassoon D, Lin V . Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell. 1989; 56(4):607-17. DOI: 10.1016/0092-8674(89)90583-7. View

Murre C, McCaw P, Baltimore D . A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989; 56(5):777-83. DOI: 10.1016/0092-8674(89)90682-x. View

Klambt C, Knust E, TIETZE K, Campos-Ortega J . Closely related transcripts encoded by the neurogenic gene complex enhancer of split of Drosophila melanogaster. EMBO J. 1989; 8(1):203-10. PMC: 400790. DOI: 10.1002/j.1460-2075.1989.tb03365.x. View

Braun T, Bober E, Tannich E, Arnold H . A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts. EMBO J. 1989; 8(3):701-9. PMC: 400865. DOI: 10.1002/j.1460-2075.1989.tb03429.x. View

10.

Edmondson D, Olson E . A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program. Genes Dev. 1989; 3(5):628-40. DOI: 10.1101/gad.3.5.628. View

11.

Mellentin J, Smith S, Cleary M . lyl-1, a novel gene altered by chromosomal translocation in T cell leukemia, codes for a protein with a helix-loop-helix DNA binding motif. Cell. 1989; 58(1):77-83. DOI: 10.1016/0092-8674(89)90404-2. View

12.

Murre C, McCaw P, Vaessin H, Caudy M, Jan L, Jan Y . Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989; 58(3):537-44. DOI: 10.1016/0092-8674(89)90434-0. View

13.

Wood W, Kao M, Gordon D, Ridgway E . Thyroid hormone regulates the mouse thyrotropin beta-subunit gene promoter in transfected primary thyrotropes. J Biol Chem. 1989; 264(25):14840-7. View

14.

Rushlow C, Hogan A, Pinchin S, Howe K, Lardelli M, Ish-Horowicz D . The Drosophila hairy protein acts in both segmentation and bristle patterning and shows homology to N-myc. EMBO J. 1989; 8(10):3095-103. PMC: 401388. DOI: 10.1002/j.1460-2075.1989.tb08461.x. View

15.

Begley C, Aplan P, Denning S, Haynes B, Waldmann T, Kirsch I . The gene SCL is expressed during early hematopoiesis and encodes a differentiation-related DNA-binding motif. Proc Natl Acad Sci U S A. 1989; 86(24):10128-32. PMC: 298658. DOI: 10.1073/pnas.86.24.10128. View

16.

Henthorn P, Kiledjian M, Kadesch T . Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif. Science. 1990; 247(4941):467-70. DOI: 10.1126/science.2105528. View

17.

Rhodes S, Konieczny S . Identification of MRF4: a new member of the muscle regulatory factor gene family. Genes Dev. 1989; 3(12B):2050-61. DOI: 10.1101/gad.3.12b.2050. View

18.

Ellis H, Spann D, Posakony J . extramacrochaetae, a negative regulator of sensory organ development in Drosophila, defines a new class of helix-loop-helix proteins. Cell. 1990; 61(1):27-38. DOI: 10.1016/0092-8674(90)90212-w. View

19.

Garrell J, Modolell J . The Drosophila extramacrochaetae locus, an antagonist of proneural genes that, like these genes, encodes a helix-loop-helix protein. Cell. 1990; 61(1):39-48. DOI: 10.1016/0092-8674(90)90213-x. View

20.

Benezra R, Davis R, Lockshon D, Turner D, Weintraub H . The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990; 61(1):49-59. DOI: 10.1016/0092-8674(90)90214-y. View