The Abd-B-like Hox Homeodomain Proteins Can Be Subdivided by the Ability to Form Complexes with Pbx1a on a Novel DNA Target

• Published in: The Journal of biological chemistry 1997-03, Vol.272 (13), p.8198-8206
• Main Authors: Shen, Wei-Fang, Rozenfeld, Sofia, Lawrence, H. Jeffrey, Largman, Corey
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; DNA - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; Drosophila Proteins; Genes, Homeobox; Homeobox A10 Proteins; Homeodomain Proteins - chemistry; Homeodomain Proteins - metabolism; Humans; Molecular Sequence Data; Pre-B-Cell Leukemia Transcription Factor 1; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins - metabolism; Structure-Activity Relationship; TATA Box; Transcription Factors - metabolism; Tryptophan; Xenopus Proteins
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.13.8198

Previous studies showed that the Hox homeodomain proteins from paralog groups 1–8 display cooperative DNA binding with the non-Hox homeodomain protein Pbx, mediated by a canonical YPWM. Although the Abd-B-like Hox proteins in paralogs 9–13 lack this sequence, Hoxb-9 and Hoxa-10 were reported to bind with Pbx1a to DNA. We show that these interactions require a tryptophan 6 amino acids N-terminal to the homeodomain. Binding site selection for Hoxb-9 with Pbx1a yielded ATGATGAC, containing a novel TTAC Hox-binding site adjacent to a Pbx site. In the presence of Pbx1a, Hoxb-9 and Hoxa-10 bound to targets containing either TTAC or TTAT. These data extend previous findings that interactions with Pbx define a Hox protein binding code for different DNA sequences across paralog groups 1 through 10. Members of the 11, 12, and 13 paralogs do not cooperatively bind DNA with Pbx1a, despite the presence of tryptophan residues N-terminal to the homeodomain in Hoxd-12 and Hoxd-13. Hoxa-11, Hoxd-12, or Hoxd-13, in the presence of Pbx1a, selected a TTAC Hox site but lacking a Pbx1a site. These data suggest that Abd-B-like Hox proteins bind to a novel TTAC site and can be divided by their cooperative binding to DNA with Pbx1a.