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Specificity landscapes unmask submaximal binding site preferences of transcription factors.

Abstract：

:We have developed Differential Specificity and Energy Landscape (DiSEL) analysis to comprehensively compare DNA-protein interactomes (DPIs) obtained by high-throughput experimental platforms and cutting edge computational methods. While high-affinity DNA binding sites are identified by most methods, DiSEL uncovered nuanced sequence preferences displayed by homologous transcription factors. Pairwise analysis of 726 DPIs uncovered homolog-specific differences at moderate- to low-affinity binding sites (submaximal sites). DiSEL analysis of variants of 41 transcription factors revealed that many disease-causing mutations result in allele-specific changes in binding site preferences. We focused on a set of highly homologous factors that have different biological roles but "read" DNA using identical amino acid side chains. Rather than direct readout, our results indicate that DNA noncontacting side chains allosterically contribute to sculpt distinct sequence preferences among closely related members of transcription factor families.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Bhimsaria D,Rodríguez-Martínez JA,Pan J,Roston D,Korkmaz EN,Cui Q,Ramanathan P,Ansari AZ

doi

10.1073/pnas.1811431115

subject

Has Abstract

pub_date

2018-11-06 00:00:00

pages

E10586-E10595

issue

45

eissn

0027-8424

issn

1091-6490

pii

1811431115

journal_volume

115

pub_type

杂志文章

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