Multi-scale chromatin state annotation using a hierarchical hidden Markov model

Nat Commun. 2017 Apr 7:8:15011. doi: 10.1038/ncomms15011.

Abstract

Chromatin-state analysis is widely applied in the studies of development and diseases. However, existing methods operate at a single length scale, and therefore cannot distinguish large domains from isolated elements of the same type. To overcome this limitation, we present a hierarchical hidden Markov model, diHMM, to systematically annotate chromatin states at multiple length scales. We apply diHMM to analyse a public ChIP-seq data set. diHMM not only accurately captures nucleosome-level information, but identifies domain-level states that vary in nucleosome-level state composition, spatial distribution and functionality. The domain-level states recapitulate known patterns such as super-enhancers, bivalent promoters and Polycomb repressed regions, and identify additional patterns whose biological functions are not yet characterized. By integrating chromatin-state information with gene expression and Hi-C data, we identify context-dependent functions of nucleosome-level states. Thus, diHMM provides a powerful tool for investigating the role of higher-order chromatin structure in gene regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms*
  • Cell Line
  • Chromatin / genetics*
  • Chromatin / metabolism
  • Gene Expression Regulation*
  • Histones / metabolism
  • Humans
  • K562 Cells
  • Markov Chains*
  • Nucleosomes / genetics*
  • Nucleosomes / metabolism
  • Polycomb-Group Proteins / genetics
  • Polycomb-Group Proteins / metabolism
  • Promoter Regions, Genetic / genetics

Substances

  • Chromatin
  • Histones
  • Nucleosomes
  • Polycomb-Group Proteins