期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 48, 页码 17140-17145出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1410569111
关键词
protein-DNA binding; nonspecific protein-DNA binding; transcriptional regulation
资金
- PhRMA Foundation Research Starter grant
- Israel Science Foundation Grant [1014/09]
- Adams Fellowship program of the Israel National Academy of Science
- Duke Translational Medicine Quality Framework postdoctoral fellowship
Until now, it has been reasonably assumed that specific base-pair recognition is the only mechanism controlling the specificity of transcription factor (TF)-DNA binding. Contrary to this assumption, here we show that nonspecific DNA sequences possessing certain repeat symmetries, when present outside of specific TF binding sites (TFBSs), statistically control TF-DNA binding preferences. We used highthroughput protein-DNAbinding assays to measure the binding levels and free energies of binding for several humanTFs to tens of thousands of short DNA sequences with varying repeat symmetries. Based on statisticalmechanicsmodeling, weidentifyanewprotein-DNAbinding mechanism induced by DNA sequence symmetry in the absence of specific base-pair recognition, and experimentally demonstrate that this mechanism indeed governs protein-DNA binding preferences.
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