Nucleosome Density ChIP-Seq Identifies Distinct Chromatin Modification Signatures Associated with MNase Accessibility

作者：Lorzadeh Alireza; Bilenky Misha; Hammond Colin; Knapp David J H F; Li Luolan; Miller Paul H; Carles Annaick; Heravi Moussavi Alireza; Gakkhar Sitanshu; Moksa Michelle; Eaves Connie J; Hirst Martin

来源：Cell Reports, 2016, 17(8): 2112-2124.

DOI：10.1016/j.celrep.2016.10.055

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.

• 出版日期2016-11-15