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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Base Sequence
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Binding Sites
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Carrier Proteins / genetics*
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DNA Breaks, Double-Stranded
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DNA Footprinting / methods*
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DNA Repair
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Enhancer Elements, Genetic
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Erythrocytes / physiology
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Erythropoiesis
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Genome, Human
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Genomics / methods*
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Humans
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Mutation
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Nuclear Proteins / genetics*
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Regulatory Sequences, Nucleic Acid*
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Repressor Proteins
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Transcription Factors / metabolism
Substances
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BCL11A protein, human
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Carrier Proteins
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Nuclear Proteins
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Repressor Proteins
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Transcription Factors