title: TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family.
abstract: The DNA-binding factor TFEB contains adjacent helix-loop-helix (HLH) and leucine zipper (LZ) domains flanked by an upstream basic region. This arrangement of interactive motifs has recently been observed in several other transcription factors and in the Myc family of oncogenes. TFEB was isolated by virtue of its binding to the major late promoter of adenovirus. DNA binding by a soluble protein was achieved by deleting a hydrophobic amino-terminal domain and permitted the structural analysis of the oligomerization and DNA-binding properties of TFEB. TFEB specifically bound DNA as both a homodimer and a heterodimer with another b-HLH-LZ protein TFE3. The LZ domain was essential for homo- or hetero-oligomerization and high-affinity DNA binding. In the absence of DNA a tetramer-sized form of TFEB was observed that dissociates to bind added DNA as a dimer. Binding by TFEB and TFE3 to related, but different, naturally occurring DNA target sequences was observed with distinct binding preferences. Analysis of basic domain residues in this family of proteins revealed a pattern of sequence conservation predictive of an interacting alpha-helical face. Common oligomerization and DNA-binding features suggest the b-HLH-LZ domain structure to define a distinct family of DNA-binding factors.
authors.affiliation: Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: D E
authors.initials: DE
authors.lastname: Fisher
authors.forename: C S
authors.initials: CS
authors.lastname: Carr
authors.forename: L A
authors.initials: LA
authors.lastname: Parent
authors.forename: P A
authors.initials: PA
authors.lastname: Sharp
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D015345:Oligonucleotide Probes; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015345:Oligonucleotide Probes; C069203:TFE3 protein, human; C064972:TFEB protein, human; D014157:Transcription Factors; D004247:DNA