Functional dissection of a transcriptionally active, target-specific Hox-Pbx complex - PubMed (original) (raw)

Functional dissection of a transcriptionally active, target-specific Hox-Pbx complex

G Di Rocco et al. EMBO J. 1997.

Abstract

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.

PubMed Disclaimer

Cited by

p160 Myb-binding protein interacts with Prep1 and inhibits its transcriptional activity.
Díaz VM, Mori S, Longobardi E, Menendez G, Ferrai C, Keough RA, Bachi A, Blasi F. Díaz VM, et al. Mol Cell Biol. 2007 Nov;27(22):7981-90. doi: 10.1128/MCB.01290-07. Epub 2007 Sep 17. Mol Cell Biol. 2007. PMID: 17875935 Free PMC article.
Cell signaling switches HOX-PBX complexes from repressors to activators of transcription mediated by histone deacetylases and histone acetyltransferases.
Saleh M, Rambaldi I, Yang XJ, Featherstone MS. Saleh M, et al. Mol Cell Biol. 2000 Nov;20(22):8623-33. doi: 10.1128/MCB.20.22.8623-8633.2000. Mol Cell Biol. 2000. PMID: 11046157 Free PMC article.
Mutation analysis and embryonic expression of the HLXB9 Currarino syndrome gene.
Hagan DM, Ross AJ, Strachan T, Lynch SA, Ruiz-Perez V, Wang YM, Scambler P, Custard E, Reardon W, Hassan S, Nixon P, Papapetrou C, Winter RM, Edwards Y, Morrison K, Barrow M, Cordier-Alex MP, Correia P, Galvin-Parton PA, Gaskill S, Gaskin KJ, Garcia-Minaur S, Gereige R, Hayward R, Homfray T. Hagan DM, et al. Am J Hum Genet. 2000 May;66(5):1504-15. doi: 10.1086/302899. Epub 2000 Apr 4. Am J Hum Genet. 2000. PMID: 10749657 Free PMC article.
Activity regulation of a Hox protein and a role for the homeodomain in inhibiting transcriptional activation.
Li X, Murre C, McGinnis W. Li X, et al. EMBO J. 1999 Jan 4;18(1):198-211. doi: 10.1093/emboj/18.1.198. EMBO J. 1999. PMID: 9878063 Free PMC article.
The subcellular localization of PBX1 and EXD proteins depends on nuclear import and export signals and is modulated by association with PREP1 and HTH.
Berthelsen J, Kilstrup-Nielsen C, Blasi F, Mavilio F, Zappavigna V. Berthelsen J, et al. Genes Dev. 1999 Apr 15;13(8):946-53. doi: 10.1101/gad.13.8.946. Genes Dev. 1999. PMID: 10215622 Free PMC article.

References

1. Development. 1993 Oct;119(2):319-38 - PubMed
1. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):739-43 - PubMed
1. EMBO J. 1996 Apr 15;15(8):1961-70 - PubMed
1. Nat Genet. 1992 Aug;1(5):319-20 - PubMed
1. Mol Cell Biol. 1991 Dec;11(12):6149-57 - PubMed

Functional dissection of a transcriptionally active, target-specific Hox-Pbx complex - PubMed (original) (raw)