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Mol. Cell. Biol., 10 1997, 5679-5687, Vol 17, No. 10
CP Chang, Y Jacobs, T Nakamura, NA Jenkins, NG Copeland and ML Cleary
The Pbx1 and Meis1 proto-oncogenes code for divergent homeodomain proteins
that are targets for oncogenic mutations in human and murine leukemias,
respectively, and implicated by genetic analyses to functionally
collaborate with Hox proteins during embryonic development and/or
oncogenesis. Although Pbx proteins have been shown to dimerize with Hox
proteins and modulate their DNA binding properties in vitro, the
biochemical compositions of endogenous Pbx-containing complexes have not
been determined. In the present study, we demonstrate that Pbx and Meis
proteins form abundant complexes that comprise a major Pbx- containing DNA
binding activity in nuclear extracts of cultured cells and mouse embryos.
Pbx1 and Meis1 dimerize in solution and cooperatively bind bipartite DNA
sequences consisting of directly adjacent Pbx and Meis half sites.
Pbx1-Meis1 heterodimers display distinctive DNA binding specificities and
cross-bind to a subset of Pbx- Hox sites, including those previously
implicated as response elements for the execution of Pbx-dependent Hox
programs in vivo. Chimeric oncoprotein E2a-Pbx1 is unable to bind DNA with
Meis1, due to the deletion of amino-terminal Pbx1 sequences following
fusion with E2a. We conclude that Meis proteins are preferred in vivo DNA
binding partners for wild-type Pbx1, a relationship that is circumvented by
its oncogenic counterpart E2a-Pbx1.
Copyright © 1997, American Society for Microbiology
Meis proteins are major in vivo DNA binding partners for wild-type but not chimeric Pbx proteins
Department of Pathology, Stanford University Medical Center, California 94305, USA.
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