Title

Range of HOX/TALE Superclass Associations and Protein Domain Requirements for HOXA13:MEIS Interaction

Document Type

Article

Publication Date

1-2005

Publication Source

Developmental Biology

Abstract

AbdB-like HOX proteins form DNA-binding complexes with the TALE superclass proteins MEIS1A and MEIS1B, and trimeric complexes have been identified in nuclear extracts that include a second TALE protein, PBX. Thus, soluble DNA-independent protein–protein complexes exist in mammals. The extent of HOX/TALE superclass interactions, protein structural requirements, and sites of in vivo cooperative interaction have not been fully explored. We show that Hoxa13 and Hoxd13 expression does not overlap with that of Meis13 in the developing limb; however, coexpression occurs in the developing male and female reproductive tracts (FRTs). We demonstrate that both HOXA13 and HOXD13 associate with MEIS1B in mammalian and yeast cells, and that HOXA13 can interact with all MEIS proteins but not more diverged TALE superclass members. In addition, the C-terminal domains (CTDs) of MEIS1A (18 amino acids) and MEIS1B (93 amino acids) are necessary for HOXA13 interaction; for MEIS1B, this domain was also sufficient. We also show by yeast two-hybrid assay that MEIS proteins can interact with anterior HOX proteins, but for some, additional N-terminal MEIS sequences are required for interaction. Using deletion mutants of HOXA13 and HOXD13, we provide evidence for multiple HOX peptide domains interacting with MEIS proteins. These data suggest that HOX:MEIS interactions may extend to non-AbdB-like HOX proteins in solution and that differences may exist in the MEIS peptide domains utilized by different HOX groups. Finally, the capability of multiple HOX domains to interact with MEIS C-terminal sequences implies greater complexity of the HOX:MEIS protein–protein interactions and a larger role for variation of HOX amino-terminal sequences in specificity of function.

Inclusive pages

457–471

ISBN/ISSN

0012-1606

Comments

Permission documentation is on file.

Publisher

Elsevier

Volume

277

Issue

2

Peer Reviewed

yes