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Molecular and Cellular Biology, November 1999, p. 7577-7588, Vol. 19, No. 11
McGill Cancer Centre,1
Division of Experimental Medicine,
Received 22 March 1999/Returned for modification 5 May
1999/Accepted 21 July 1999
HOX, PBX, and MEIS transcription factors bind DNA through a
homeodomain. PBX proteins bind DNA cooperatively as heterodimers with
MEIS family members and also with HOX proteins from paralog groups 1 to
10. MEIS proteins cooperatively bind DNA with ABD-B class HOX proteins
of groups 9 and 10. Here, we examine aspects of dimeric and
higher-order interactions between these three homeodomain classes. The
most significant results can be summarized as follows. (i) Most of PBX
N terminal to the homeodomain is required for efficient cooperative
binding with HOXD4 and HOXD9. (ii) MEIS and PBX proteins form
higher-order complexes on a heterodimeric binding site. (iii) Although
MEIS does not cooperatively bind DNA with ANTP class HOX proteins, it
does form a trimer as a non-DNA-binding partner with DNA-bound
PBX-HOXD4. (iv) The N terminus of HOXD4 negatively regulates trimer
formation. (v) MEIS forms a similar trimer with DNA-bound
PBX-HOXD9. (vi) A related trimer (where MEIS is a non-DNA-binding
partner) is formed on a transcriptional promoter within the cell.
(vii) We observe an additional trimer class involving non-DNA-bound PBX
and DNA-bound MEIS-HOXD9 or MEIS-HOXD10 heterodimers that is enhanced
by mutation of the PBX homeodomain. (viii) In this latter trimer, PBX
is likely to contact both MEIS and HOXD9/D10. (ix) The stability of DNA
binding by all trimers is enhanced relative to the heterodimers. These
findings suggest novel functions for PBX and MEIS in modulating the
function of DNA-bound MEIS-HOX and PBX-HOX heterodimers, respectively.
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
PBX and MEIS as Non-DNA-Binding Partners in
Trimeric Complexes with HOX Proteins
*
Corresponding author. Mailing address: McGill Cancer
Centre, McGill University, Montreal, Quebec, Canada H3G 1Y6. Phone:
(514) 398-8937. Fax: (514) 398-6769. E-mail:
mfeather{at}med.mcgill.ca.
Molecular and Cellular Biology, November 1999, p. 7577-7588, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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