The Abd-B-like Hox homeodomain proteins can be subdivided by the ability to form complexes with Pbx1a on a novel DNA target.
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 ATGATTTACGAC, 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.
Shen
W F
WF
Department of Medicine, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California 94121, USA.
Rozenfeld
S
S
Lawrence
H J
HJ
Largman
C
C
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D029721:Drosophila Proteins; D005801:Genes, Homeobox; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D016385:TATA Box; D014157:Transcription Factors / Q000378:metabolism; D014364:Tryptophan; D029867:Xenopus Proteins
C062393:Abd-B proteins, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C484298:HOXA11 protein, human; C491257:HOXB9 protein, human; C513184:HOXD13 protein, human; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C094041:Hoxa11 protein, mouse; C491256:Hoxb9 protein, Xenopus; C490943:Hoxd12 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C083400:PBX1 protein, human; C092119:Hoxa10 protein, mouse; D014364:Tryptophan; D004247:DNA