Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.
Multiple histone modifications act in concert to determine genome functions, producing combinatorial chromatin "states". We used unsupervised, multivariate HMM machine learning to segment the genome based on the combinatorial patterns of 18 histone modifications in S2 and BG3 cells (52). This produced a nine state intensity-based model (continuous model states c1 to c9) reflecting major chromatin states, as well as a 30 state model that identifies combinatorial patterns at a finer resolution (discrete model states d1 to d30).
|1||Promoter and TSS|
|3||Regulatory regions (enhancers)|
|5||Active genes on the Male X|
|8||Heterochromatin-like embedded in euchromatin|
|30||9||Transcriptionally silent, intergenic|
Kharchenko PV., et al.
Comprehensive analysis of the chromatin landscape in Drosophila melanogaster.
Nature Volume: 471, Pages: 480-485 (24 March 2011)