Mapping cell type-specific transcriptional enhancers using high affinity, lineage-specific Ep300 bioChIP-seq
- Boston Children's Hospital, United States
- Shanghai University of Traditional Chinese Medicine, China
- Chinese Academy of Sciences, China
Abstract
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 indentify 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.
Data availability
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Mapping cell type-specific transcriptional enhancers using high affinity, lineage-specific p300 bioChIP-seqPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE88789).
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Transcription Factor Binding Sites by ChIP-seq from ENCODE/LICRPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE36027).
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ChIP-seq from heart (ENCSR646GHA)Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE82850).
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ChIP-seq from heart (ENCSR123MLY)Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM2191196).
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ChIP-seq Accurately Predicts Tissue-Specific Activity of EnhancersPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE13845).
Article and author information
Author details
Funding
National Institutes of Health (U01HL098166; HL095712)
- William T Pu
American Heart Association (12EIA8440003)
- William T Pu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experiments were performed under protocols approved by the Boston Children's Hospital Animal Care and Use Committee (protocols 13-08-2460R and 13-12-2601).
Reviewing Editor
- Deepak Srivastava, Gladstone Institutes, United States
Publication history
- Received: October 2, 2016
- Accepted: January 23, 2017
- Accepted Manuscript published: January 25, 2017 (version 1)
- Version of Record published: February 7, 2017 (version 2)
- Version of Record updated: April 11, 2017 (version 3)
Copyright
© 2017, Zhou et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mapping cell type-specific transcriptional enhancers using high affinity, lineage-specific Ep300 bioChIP-seq
eLife 6:e22039.
https://doi.org/10.7554/eLife.22039
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