期刊
CELL REPORTS
卷 17, 期 8, 页码 2112-2124出版社
CELL PRESS
DOI: 10.1016/j.celrep.2016.10.055
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资金
- Frederick Banting and Charles Best Canada
- Canadian Epigenetics, Environment and Health Research Consortium [CIHR EP1-120589 CIHR-262119/Genome BC C34GBM]
- Terry Fox Research Institute Program [TFRI-122869]
- Terry Fox Research Institute [TFRI-1039]
Nucleosome position, density, and post-translational modification are widely accepted components of mechanisms regulating DNA transcription but still incompletely understood. We present a modified native ChIP-seq method combined with an analytical framework that allows MNase accessibility to be integrated with histone modification profiles. Application of this methodology to the primitive (CD34+) subset of normal human cord blood cells enabled genomic regions enriched in one versus two nucleo-somes marked by histone 3 lysine 4 trimethylation (H3K4me3) and/or histone 3 lysine 27 trimethylation (H3K27me3) to be associated with their transcriptional and DNA methylation states. From this analysis, we defined four classes of promoter-specific profiles and demonstrated that a majority of bivalent marked promoters are heterogeneously marked at a singlecell level in this primitive cell type. Interestingly, extension of this approach to human embryonic stem cells revealed an altered relationship between chromatin modification state and nucleosome content at promoters, suggesting developmental stage-specific organization of histone methylation states.
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