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Functional footprinting of regulatory DNA.

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.

SUBMITTER: Vierstra J

PROVIDER: S-EPMC5381659 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Functional footprinting of regulatory DNA.

Vierstra Jeff J Reik Andreas A Chang Kai-Hsin KH Stehling-Sun Sandra S Zhou Yuanyue Y Hinkley Sarah J SJ Paschon David E DE Zhang Lei L Psatha Nikoletta N Bendana Yuri R YR O'Neil Colleen M CM Song Alexander H AH Mich Andrea K AK Liu Pei-Qi PQ Lee Gary G Bauer Daniel E DE Holmes Michael C MC Orkin Stuart H SH Papayannopoulou Thalia T Stamatoyannopoulos George G Rebar Edward J EJ Gregory Philip D PD Urnov Fyodor D FD Stamatoyannopoulos John A JA

Nature methods 20150831 10

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 downstre ...[more]

PMID: 26322838

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