title: Pituitary homeodomain transcription factors HESX1 and PROP1 form a heterodimer on the inverted TAAT motif.
abstract: The development and differentiation of the pituitary gland progress through spatial and temporal expressions of many transcription factors. Transcription factor HESX1, which begins to be expressed in the Rathke's pouch at the early stage of pituitary development, acts as a transcription repressor. Another transcription factor, PROP1, which is a pituitary-specific factor and important for the determination of the differentiation of pituitary hormone-producing cells, appears later than HESX1 and is assumed to block the action of HESX1. Both factors are members of the homeodomain family, and the amino acid residue at the 50th position of the homeodomain is glutamine (Gln-50). We recently observed that both factors share the same target sequence through different binding profiles. Hence, using random oligonucleotides and an electrophoretic mobility-shift assay, we have examined the DNA-binding preference of HESX1 by a determination of its binding sequence. HESX1 binds as a monomer to a TAATT motif but not to a TAAT motif. In the presence of PROP1, HESX1 develops to bind to an inverted TAAT motif by forming a heterodimer. Thus, the formation of a heterodimer between HESX1 and PROP1 provides a condition in which, in the early pituitary primordium, HESX1 alters its repressive role to an active one by forming a heterodimer with newly appearing PROP1 so that PROP1 finally replaces HESX1 to advance to the middle stage of pituitary development.
authors.affiliation: Laboratory of Molecular Biology and Gene Regulation, Graduate School of Agriculture, Meiji University, Kawasaki, Kanagawa 214-8571, Japan. yukato@isc.meiji.ac.jp
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.forename: Fuyuko
authors.initials: F
authors.lastname: Kimoto
authors.forename: Takao
authors.initials: T
authors.lastname: Susa
authors.forename: Michie
authors.initials: M
authors.lastname: Nakayama
authors.forename: Akio
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Takako
authors.initials: T
authors.lastname: Kato
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012097:Repressor Proteins; D013552:Swine; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C489733:Hesx1 protein, mouse; D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D012097:Repressor Proteins; D014157:Transcription Factors