title: Retinoic acid-responsive enhancers located 3' of the Hox A and Hox B homeobox gene clusters. Functional analysis.
abstract: Homeobox genes control the spatial identity and differentiation of tissues in the developing vertebrate embryo. Retinoids are signaling molecules involved in the regulation of Hox genes. We previously identified a 3' enhancer called the RAIDR5, which contained a DR5 retinoic acid response element (RARE) and was responsible for the retinoic acid (RA)-associated expression of the murine Hoxa-1 gene in teratocarcinoma cells. We demonstrate that a similar enhancer, which contains a DR5 RARE, is located at a DNase I-hypersensitive site 3' of the murine Hoxb-1 gene. This enhancer, the Hoxb-1 RAIDR5, regulates the RA responsiveness of the Hoxb-1 gene and is different in location and sequence from the RA-regulated 3' Hoxb-1 enhancers previously described. Several DNA elements within the murine Hoxa-1 RA-inducible RAIDR5 enhancer, including the DR5 RARE, conserved element (CE) 1, and CE2, are conserved in the murine Hoxb-1 RAIDR5 enhancer, the human homolog of Hoxa-1, and in the chicken Hoxb-1 gene. Gel shifts show that the CE2 sequence TATTTACTCA binds an RA-inducible factor, while UV cross-linking indicates that a 170-kDa protein binds to this sequence. Thus, the Hoxa-1 and Hoxb-1 genes possess 3' enhancers with similar sequences through which their expression and responsiveness to endogenous retinoids are controlled.
authors.affiliation: Department of Pharmacology, Cornell University Medical College, New York, New York 10021, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Langston
authors.forename: J R
authors.initials: JR
authors.lastname: Thompson
authors.forename: L J
authors.initials: LJ
authors.lastname: Gudas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D005801:Genes, Homeobox / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D000099261:Homeobox A1 Protein
chemical_list: D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D014212:Tretinoin; D000099261:Homeobox A1 Protein; C101121:HOXB1 homeodomain protein