title: Stra13 homodimers repress transcription through class B E-box elements.
abstract: A mammalian basic helix-loop-helix protein known variably as Stra13, Sharp2, and Dec1 has been implicated in cell activation, proliferation, and differentiation. Indeed, Stra13 null mice develop age-induced autoimmunity as a result of impaired T-lymphocyte activation, leading ultimately to the accumulation of autoreactive T-cells and B-cells. Stra13 is expressed in embryonic as well as adult tissues derived from neuroectoderm, mesoderm, and endoderm and has been associated with response to hypoxia, suggesting a complex role for this protein and the highly related Sharp1/Dec2 protein in homeostatic regulation. Whereas Stra13 is known to regulate many important cellular functions and is known to cross-regulate biological responses to other basic helix-loop-helix containing transcription factors, including c-Myc and USF, it is unclear if this protein binds directly to DNA. Indeed, the basic domain of Stra13 contains a proline residue at an unprecedented position. Herein, we have determined that Stra13 binds with high affinity to CACGTG class B E-box elements as a homodimer with preference for elements preceded by T and/or followed by A residues. In addition, transient transfection experiments reveal that Stra13 represses transcription when bound to these and related sites. Our data suggest that Stra13 regulates cellular functions through antagonism of E-box activator proteins and also through active repression from E-box elements.
authors.affiliation: Programs in Cancer Research and Developmental Biology, The Hospital for Sick Children, Toronto, Ontario M5G-1X8, Canada.
authors.forename: Benoit
authors.initials: B
authors.lastname: St-Pierre
authors.forename: Grace
authors.initials: G
authors.lastname: Flock
authors.forename: Eldad
authors.initials: E
authors.lastname: Zacksenhaus
authors.forename: Sean E
authors.initials: SE
authors.lastname: Egan
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D019556:COS Cells; D015342:DNA Probes; D019281:Dimerization; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D010957:Plasmids; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015342:DNA Probes; D018398:Homeodomain Proteins; D012097:Repressor Proteins; C491539:Bhlhe40 protein, mouse