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Full Abstracts – REGULATION OF GENE EXPRESSION
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Unlocking specificity: Cofactor binding reveals latent differences in DNA binding specificity between Hox proteins.
Matthew Slattery
1,2
, Todd
Riley
3,4
, Peng Liu
4,5
, Namiko Abe
2
, Pilar Gomez-Alcala
3,6
, Iris Dror
7
, Tianyin Zhou
7
, Remo Rohs
7
, Barry Honig
4,5
, Harmen Bussemaker
3,4
, Richard Mann
2
. 1)
University of Chicago, Chicago, IL; 2) Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY; 3) Department of
Biological Sciences, Columbia University, New York, NY; 4) Center for Computational Biology and Bioinformatics, Columbia University, New York, NY;
5) Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY; 6) Department of
Electrical Engineering, Columbia University, New York, NY; 7) Molecular and Computational Biology Program, Department of Biological Sciences,
University of Southern California, Los Angeles, CA.
Members of transcription factor families typically have similar DNA binding specificities yet execute unique functions in vivo. Transcription factors often
bind DNA as multiprotein complexes, raising the possibility that complex formation might modify their DNA binding specificities. To test this hypothesis,
an experimental platform was developed, termed SELEX-seq, that can be used to determine the relative affinities to any DNA sequence for any transcription
factor complex. Applying this method to all eight Drosophila Hox proteins revealed that they obtain novel recognition properties when they bind DNA with
the cofactor Extradenticle (Exd). Exd-Hox specificities group into three main classes that obey Hox gene collinearity rules and DNA structure predictions
suggest that anterior and posterior Hox proteins prefer DNA sequences with distinct minor groove topographies. Together, these data suggest that emergent
DNA recognition properties revealed by interactions with cofactors contribute to transcription factor specificities
in vivo
.