Retinoic Acid-responsive Enhancers Located 3′ of the Hox A and Hox B Homeobox Gene Clusters

• Published in: The Journal of biological chemistry Vol. 272; no. 4; p. 2167
• Main Authors: Alexander W. Langston, James R. Thompson, Lorraine J. Gudas
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 24.01.1997
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.4.2167

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 RAIDR 5 , 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 DR 5 RARE, is located at a DNase I-hypersensitive site 3′ of the murine Hoxb-1 gene. This enhancer, the Hoxb-1 RAIDR 5 , 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 RAIDR 5 enhancer, including the DR 5 RARE, conserved element (CE) 1, and CE2, are conserved in the murine Hoxb-1 RAIDR 5 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.