Nature Methods: Functional footprinting of regulatory DNA

• Jeff Vierstra,^{1, n1}Andreas Reik,^{2, n1}Kai-Hsin Chang,^3,
• Sandra Stehling-Sun,^1,Yuanyue Zhou,^2,Sarah J Hinkley,^2,
• David E Paschon,^2,Lei Zhang,^2,Nikoletta Psatha,^3,
• Yuri R Bendana,^2,Colleen M O'Neil,^2,Alexander H Song,^2,
• Andrea K Mich,^2,Pei-Qi Liu,^2,Gary Lee,^2,
• Daniel E Bauer,^4,Michael C Holmes,^2,Stuart H Orkin,^4,
• Thalia Papayannopoulou,^3,George Stamatoyannopoulos,⁵
• dward J Rebar,^2,Philip D Gregory,²Fyodor D Urnov^2,
• & John A Stamatoyannopoulos^{1, 6,}

• Affiliations
• Contributions
• Corresponding authors

Journal name:

Nature Methods

Year published:

(2015)

DOI:

doi:10.1038/nmeth.3554

Received

25 March 2015 Accepted  30 July 2015

Published online

31 August 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.    

http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.3554.html