title: 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.
authors: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors: Jeff
authors: http://orcid.org/0000-0001-6406-8563
authors: J
authors: Vierstra
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Andreas
authors: A
authors: Reik
authors: Department of Medicine, Division of Hematology, University of Washington, Seattle, Washington, USA.
authors: Kai-Hsin
authors: KH
authors: Chang
authors: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors: Sandra
authors: S
authors: Stehling-Sun
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Yuanyue
authors: Y
authors: Zhou
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Sarah J
authors: SJ
authors: Hinkley
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: David E
authors: DE
authors: Paschon
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Lei
authors: L
authors: Zhang
authors: Department of Medicine, Division of Hematology, University of Washington, Seattle, Washington, USA.
authors: Nikoletta
authors: N
authors: Psatha
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Yuri R
authors: YR
authors: Bendana
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Colleen M
authors: CM
authors: O'Neil
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Alexander H
authors: AH
authors: Song
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Andrea K
authors: AK
authors: Mich
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Pei-Qi
authors: PQ
authors: Liu
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Gary
authors: G
authors: Lee
authors: Boston Children's Hospital, Division of Hematology/Oncology, Boston, Massachusetts, USA.
authors: Daniel E
authors: DE
authors: Bauer
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Michael C
authors: MC
authors: Holmes
authors: Boston Children's Hospital, Division of Hematology/Oncology, Boston, Massachusetts, USA.
authors: Stuart H
authors: SH
authors: Orkin
authors: Department of Medicine, Division of Hematology, University of Washington, Seattle, Washington, USA.
authors: Thalia
authors: T
authors: Papayannopoulou
authors: Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
authors: George
authors: G
authors: Stamatoyannopoulos
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Edward J
authors: EJ
authors: Rebar
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Philip D
authors: PD
authors: Gregory
authors: Sangamo BioSciences, Pt. Richmond, California, USA.
authors: Fyodor D
authors: FD
authors: Urnov
authors: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.|Department of Medicine, Division of Oncology, University of Washington, Seattle, Washington, USA.
authors: John A
authors: JA
authors: Stamatoyannopoulos
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D018983:DNA Footprinting / Q000379:methods*; D004260:DNA Repair; D004742:Enhancer Elements, Genetic; D004912:Erythrocytes / Q000502:physiology; D004920:Erythropoiesis; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors