Functional footprinting of regulatory DNA

J Vierstra, A Reik, KH Chang, S Stehling-Sun, Y Zhou… - Nature …, 2015 - nature.com
J Vierstra, A Reik, KH Chang, S Stehling-Sun, Y Zhou, SJ Hinkley, DE Paschon, L Zhang…
Nature methods, 2015nature.com
Regulatory regions harbor multiple transcription factor (TF) recognition sites; however, the
contribution of individual sites to regulatory function remains challenging to define. We
describe an approach that exploits the error-prone nature of genome editing–induced
double-strand break repair to map functional elements within regulatory DNA at nucleotide
resolution. We demonstrate the approach on a human erythroid enhancer, revealing single
TF recognition sites that gate the majority of downstream regulatory function.
Abstract
Regulatory regions harbor multiple transcription factor (TF) recognition sites; however, the contribution of individual sites to regulatory function remains challenging to define. We describe an approach that exploits the error-prone nature of genome editing–induced double-strand break repair to map functional elements within regulatory DNA at nucleotide resolution. We demonstrate the approach on a human erythroid enhancer, revealing single TF recognition sites that gate the majority of downstream regulatory function.
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