Premium
Functional dissection of a transcriptionally active, target‐specific Hox–Pbx complex
Author(s) -
Di Rocco Giuliana,
Mavilio Fulvio,
Zappavigna Vincenzo
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.12.3644
Subject(s) - hox gene , biology , dissection (medical) , gene , genetics , gene expression , anatomy
Hox genes control cell fates and specify regional identities in vertebrate development. Hox proteins show a relaxed DNA‐binding selectivity in vitro , suggesting that functional specificity is achieved in vivo through the action of transcriptional co‐factors. Pbx proteins are good candidates for such a role, on the basis of both genetic and biochemical evidence. We report that the human Pbx1 and HOXB1 proteins can cooperatively activate transcription through a genetically characterized Hox target, i.e. an autoregulatory element directing spatially restricted expression of the murine Hoxb‐1 gene (b1‐ARE) in the developing hindbrain. On the b1‐ARE, only a restricted subset of HOX proteins (HOXA1, HOXB1, HOXA2) are able to bind cooperatively with Pbx1 and activate transcription. Selective recognition of the b1‐ARE is mediated by the N‐terminal region of the HOX homeodomain. The DNA‐binding and protein–protein interaction functions of HOXB1 and Pbx1 are all necessary for the assembly of a transcriptionally active complex on the b1‐ARE. Functional dissection of the complex allowed the localization of the main activation domain in the HOXB1 N‐terminal region, and of an additional one in the C‐terminal region of Pbx1 contained in the Pbx1a but not in the alternatively spliced Pbx1b isoform. Our results indicate that Pbx1 acts as a transcriptional co‐factor of Hox proteins, allowing selective recognition and cooperative activation of regulatory target sequences.