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

eLife

Lina Zhang¹  Fei Gu²  Qing Ma²  William T Pu²  Sean M Stevens²  Brynn N Akerberg²  Pingzhu Zhou²  Kai Li²  Zhiqiang Lin²  Aibin He³  Bin Zhou⁴ 

[1] Department of Biochemistry, Institute of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China;Department of Cardiology, Boston Children’s Hospital, Boston, United States;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;

关键词: transcriptional enhancer;    endothelial cell;    angiogenesis;    p300;   

DOI  :  10.7554/eLife.22039

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown