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Elife. 2017 Jan 25;6. pii: e22039. doi: 10.7554/eLife.22039.

Mapping cell type-specific transcriptional enhancers using high affinity, lineage-specific Ep300 bioChIP-seq.

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Department of Cardiology, Boston Children's Hospital, Boston, United States.
Department of Biochemistry, Institute of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
State Key Laboratory of Cell Biology, CAS center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
Harvard Stem Cell Institute, Harvard University, Cambridge, United States.
Contributed equally


Understanding the mechanisms that regulate cell type-specific transcriptional programs requires developing a lexicon of their genomic regulatory elements. We developed a lineage-selective method to map transcriptional enhancers, regulatory genomic regions that activate transcription, in mice. Since most tissue-specific enhancers are bound by the transcriptional co-activator Ep300, we used Cre-directed, lineage-specific Ep300 biotinylation and pulldown on immobilized streptavidin followed by next generation sequencing of co-precipitated DNA to identify lineage-specific enhancers. By driving this system with lineage-specific Cre transgenes, we mapped enhancers active in embryonic endothelial cells/blood or skeletal muscle. Analysis of these enhancers identified new transcription factor heterodimer motifs that likely regulate transcription in these lineages. Furthermore, we identified candidate enhancers that regulate adult heart- or lung- specific endothelial cell specialization. Our strategy for tissue-specific protein biotinylation opens new avenues for studying lineage-specific protein-DNA and protein-protein interactions.


angiogenesis; chromosomes; developmental biology; endothelial cell; genes; mouse; p300; stem cells; transcriptional enhancer

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