title: A tiered hidden Markov model characterizes multi-scale chromatin states.
abstract: Precise characterization of chromatin states is an important but difficult task for understanding the regulatory role of chromatin. A number of computational methods have been developed with varying levels of success. However, a remaining challenge is to model epigenomic patterns over multi-scales, as each histone mark is distributed with its own characteristic length scale. We developed a tiered hidden Markov model and applied it to analyze a ChIP-seq dataset in human embryonic stem cells. We identified a two-tier structure containing 15 distinct bin-level chromatin states grouped into three domain-level states. Whereas the bin-level states capture the local variation of histone marks, the domain-level states detect large-scale variations. Compared to bin-level states, the domain-level states are more robust and coherent. We also found active regions in intergenic regions that upon closer examination were expressed non-coding RNAs and pseudogenes. These results provide insights into an additional layer of complexity in chromatin organization.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA. larsonj5@gene.com
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Larson
authors.forename: Curtis
authors.initials: C
authors.lastname: Huttenhower
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.forename: Guo-Cheng
authors.initials: GC
authors.lastname: Yuan
mesh_terms: D001665:Binding Sites; D002843:Chromatin / Q000235:genetics* / Q000648:ultrastructure; D019295:Computational Biology; D004247:DNA / Q000737:chemistry; D021901:DNA, Intergenic / Q000737:chemistry / Q000648:ultrastructure; D053595:Embryonic Stem Cells / Q000737:chemistry / Q000166:cytology*; D044127:Epigenesis, Genetic; D006657:Histones / Q000737:chemistry; D006801:Humans; D008390:Markov Chains; D022661:RNA, Untranslated / Q000235:genetics*
chemical_list: D002843:Chromatin; D021901:DNA, Intergenic; D006657:Histones; D022661:RNA, Untranslated; D004247:DNA