Repression by HoxA7 is mediated by the homeodomain and the modulatory action of its N-terminal-arm residues.

AUTOR(ES)

Schnabel, C A

RESUMO

Hox genes encode homeodomain-containing proteins that are presumed to control spatial patterning during murine embryogenesis through their actions as transcriptional regulatory proteins. In this study, we have investigated the transcriptional function of a prototypic member of this family, HoxA7. We demonstrate that HoxA7 function as a potent transcriptional repressor and that its action as such requires several domains, including both activator and repressor regions. The repressor regions are contained within the homeodomain and a C-terminal acidic region, both of which are well conserved among members of the Hox family. Accordingly, we show that two other members of this family also function as repressors, although they vary in their relative repressor potency. Finally, we explore the novel observation that the homeodomain of HoxA7 functions as a transcriptional repressor domain. We show that the homeodomain compared with two other DNA-binding domains, is unique in its ability to function as a repressor domain and that repression requires conserved residues, in helix III. We further show that residues in the N-terminal arm of the homeodomain contribute to the differential repressor actions of various Hox proteins. These findings demonstrate that the transcriptional function of HoxA7 and possibility of Hox proteins in general is determined by their unique combination of conserved and nonconserved regions as well as through the complex actions of their homeodomains.

Documentos Relacionados

• Functional differences between HOX proteins conferred by two residues in the homeodomain N-terminal arm.
• Transformation of myeloid progenitors by MLL oncoproteins is dependent on Hoxa7 and Hoxa9
• A role for the Msx-1 homeodomain in transcriptional regulation: residues in the N-terminal arm mediate TATA binding protein interaction and transcriptional repression.
• Retention by the endoplasmic reticulum of rotavirus VP7 is controlled by three adjacent amino-terminal residues.
• DNA binding specificity of the Arc and Mnt repressors is determined by a short region of N-terminal residues.