Functional footprinting of regulatory DNA.
Jeff VierstraAndreas ReikKai-Hsin ChangSandra Stehling-SunYuanyue ZhouSarah J HinkleyDavid E PaschonLei ZhangNikoletta PsathaYuri R BendanaColleen M O'NeilAlexander H SongAndrea K MichPei-Qi LiuGary LeeDaniel E BauerMichael C HolmesStuart H OrkinThalia PapayannopoulouGeorge StamatoyannopoulosEdward J RebarPhilip D GregoryFyodor D UrnovJohn A StamatoyannopoulosPublished in: Nature methods (2015)
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.