Nucleic Acids Research, Vol 24, Issue 12 2288-2294, Copyright © 1996 by Oxford University Press
PS Knoepfler, Q Lu and MP Kamps
Heterodimers between the Pbx/Exd and Hox/HOM-C classes of homeodomain
proteins bind regulatory elements in tissue-specific and developmentally
regulated genes. In this work, we characterize the half- site bound by both
Pbx1 and Hox proteins on a prototypic element (TGATTAAT) and determine how
the orientation of the Hox protein contributes to the DNA binding
specificity of Pbx-Hox heterodimers. We demonstrate that the Hox protein
binds the 3' TAAT sequence as its recognition core and exhibits
sequence-specific binding at positions 3' to the TAAT core. Unfavored
sequences at this position, such as two cytosines, abrogate binding to the
element. The upstream Pbx1 core sequence, TGAT, must immediately juxtapose
the Hox core. This geometry maintains the preference of Hox/HOM-C proteins
for a T base at position -1, as T represents the fourth position of the
Pbx1 core, and suggests that this T base is bound by both Pbx1 and Hox
proteins, Pbx1 binding in the major grove and the Hox protein binding in
the minor grove. Pbx1 also exhibits base selectivity 5' to its TGAT
recognition sequence.
ARTICLES
Pbx-1 Hox heterodimers bind DNA on inseparable half-sites that permit intrinsic DNA binding specificity of the Hox partner at nucleotides 3' to a TAAT motif
Department of Pathology, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA.
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