mTFE3, an X-linked transcriptional activator containing basic helix-loop-helix and zipper domains, utilizes the zipper to stabilize both DNA binding and multimerization

Southwestern (DNA-protein) screening of a murine L-cell cDNA library by using a probe for the microE3 site in the immunoglobulin heavy-chain enhancer yielded a clone, mTFE3, which is a member of the subset of basic helix-loop-helix (BHLH) proteins that also contain a leucine zipper (ZIP). Since the individual contribution of these domains is not well understood for proteins which contain them both, mutational analyses were performed to assess the functional roles of the HLH and ZIP regions for DNA binding and multimerization. The HLH region is stringently required for DNA binding but not for multimerization. The ZIP region is not stringently required for binding or multimerization, but stabilizes both multimer formation and DNA binding. A high degree of conservation at both the amino acid and nucleotide levels between the human transcription factor TFE3 and mTFE3 suggests that mTFE3 is the murine homolog of human TFE3. By using fluorescent in situ hybridization, mTFE3 was mapped to mouse chromosome X in band A2, which is just below the centromere. We show that in addition to the immunoglobulin heavy-chain microE3 site, mTFE3 binds to transcriptional elements important for lymphoid-specific, muscle-specific, and ubiquitously expressed genes. Binding of mTFE3 to DNA induces DNA bending.

[1]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[2]  J. Puck,et al.  The gene encoding human TFE3, a transcription factor that binds the immunoglobulin heavy-chain enhancer, maps to Xp11.22. , 1991, Genomics.

[3]  T. Kadesch,et al.  The leucine zipper of TFE3 dictates helix-loop-helix dimerization specificity. , 1991, Genes & development.

[4]  G. Prendergast,et al.  Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. , 1991, Science.

[5]  H. Weintraub,et al.  Sequence-specific DNA binding by the c-Myc protein. , 1990, Science.

[6]  R. Roeder,et al.  The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. , 1990, Genes & development.

[7]  A. Jauch,et al.  Molecular cytotaxonomy of primates by chromosomal in situ suppression hybridization. , 1990, Genomics.

[8]  D C Ward,et al.  Differential distribution of long and short interspersed element sequences in the mouse genome: chromosome karyotyping by fluorescence in situ hybridization. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[9]  R. Tjian,et al.  Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. , 1990, Genes & development.

[10]  K. Calame,et al.  Ig/EBP-1: a ubiquitously expressed immunoglobulin enhancer binding protein that is similar to C/EBP and heterodimerizes with C/EBP. , 1990, Genes & development.

[11]  P. Sharp,et al.  A helix-loop-helix protein related to the immunoglobulin E box-binding proteins , 1990, Molecular and cellular biology.

[12]  D. Baltimore,et al.  Mutations that disrupt DNA binding and dimer formation in the E47 helix-loop-helix protein map to distinct domains. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[13]  L. Su,et al.  TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif. , 1990, Genes & development.

[14]  A. Travers,et al.  Why bend DNA? , 1990, Cell.

[15]  H. Edenberg,et al.  cis-acting sequences involved in protein binding and in vitro transcription of the human alcohol dehydrogenase gene ADH2. , 1990, The Journal of biological chemistry.

[16]  G Hermanson,et al.  High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. , 1990, Science.

[17]  D. Lockshon,et al.  MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer , 1989, Cell.

[18]  B. Wold,et al.  Muscle creatine kinase sequence elements regulating skeletal and cardiac muscle expression in transgenic mice , 1989, Molecular and cellular biology.

[19]  R. Tjian,et al.  Leucine repeats and an adjacent DNA binding domain mediate the formation of functional cFos-cJun heterodimers. , 1989, Science.

[20]  S. McKnight,et al.  The DNA binding domain of the rat liver nuclear protein C/EBP is bipartite. , 1989, Science.

[21]  T. Curran,et al.  Parallel association of Fos and Jun leucine zippers juxtaposes DNA binding domains. , 1989, Science.

[22]  David Baltimore,et al.  A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins , 1989, Cell.

[23]  C. Dang,et al.  Involvement of the 'leucine zipper' region in the oligomerization and transforming activity of human c-myc protein , 1989, Nature.

[24]  C. Peterson,et al.  Proteins binding to site C2 (muE3) in the immunoglobulin heavy-chain enhancer exist in multiple oligomeric forms , 1989, Molecular and cellular biology.

[25]  C. Peterson,et al.  Purified mu EBP-E binds to immunoglobulin enhancers and promoters , 1988, Molecular and cellular biology.

[26]  S. McKnight,et al.  Isolation of a recombinant copy of the gene encoding C/EBP. , 1988, Genes & development.

[27]  L. Su,et al.  Identification and characterization of two functional domains within the murine heavy-chain enhancer , 1988, Molecular and cellular biology.

[28]  D. Sigman,et al.  Footprinting DNA-protein complexes in situ following gel retardation assays using 1,10-phenanthroline-copper ion: Escherichia coli RNA polymerase-lac promoter complexes. , 1987, Biochemistry.

[29]  S. Eaton,et al.  Multiple DNA sequence elements are necessary for the function of an immunoglobulin heavy chain promoter. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[30]  D. Baltimore,et al.  Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. , 1987, Science.

[31]  C. Peterson,et al.  Binding in vitro of multiple cellular proteins to immunoglobulin heavy-chain enhancer DNA , 1986, Molecular and cellular biology.

[32]  David Baltimore,et al.  Multiple nuclear factors interact with the immunoglobulin enhancer sequences , 1986, Cell.

[33]  G. Church,et al.  B lineage--specific interactions of an immunoglobulin enhancer with cellular factors in vivo. , 1985, Science.

[34]  Hen-Ming Wu,et al.  The locus of sequence-directed and protein-induced DNA bending , 1984, Nature.

[35]  D. Ward,et al.  Detection of viral genomes in cultured cells and paraffin-embedded tissue sections using biotin-labeled hybridization probes. , 1983, Virology.

[36]  S. Ohno,et al.  Ancient Linkage Groups and Frozen Accidents , 1973, Nature.

[37]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[38]  D. Housman,et al.  Rapid physical mapping of cloned DNA on banded mouse chromosomes by fluorescence in situ hybridization. , 1992, Genomics.

[39]  R. Eisenman,et al.  Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. , 1991, Science.

[40]  K. Calame.  Immunoglobulin gene transcription: molecular mechanisms. , 1989, Trends in genetics : TIG.

[41]  A. T. Sumner,et al.  Mammalian chromosome banding--an expression of genome organization. , 1989, Trends in genetics : TIG.

[42]  A. Edelman,et al.  Protein serine/threonine kinases. , 1987, Annual review of biochemistry.

[43]  D. Adler,et al.  Isolation and characterization of two repetitive DNA fragments located near the centromere of the mouse X chromosome. , 1985, Cytogenetics and cell genetics.