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Ann Appl Stat. 2016 Mar;10(1):506-526. Epub 2016 Mar 25.

CHANGE POINT ANALYSIS OF HISTONE MODIFICATIONS REVEALS EPIGENETIC BLOCKS LINKING TO PHYSICAL DOMAINS.

Author information

1
Department of Biostatistics and Genetics, University of North Carolina, Chapel Hill, NC 27599.
2
Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520.
3
Department of Biostatistics, Yale School of Public Health, New Haven, CT 06520.

Abstract

Histone modification is a vital epigenetic mechanism for transcriptional control in eukaryotes. High-throughput techniques have enabled whole-genome analysis of histone modifications in recent years. However, most studies assume one combination of histone modification invariantly translates to one transcriptional output regardless of local chromatin environment. In this study we hypothesize that, the genome is organized into local domains that manifest similar enrichment pattern of histone modification, which leads to orchestrated regulation of expression of genes with relevant biological functions. We propose a multivariate Bayesian Change Point (BCP) model to segment the Drosophila melanogaster genome into consecutive blocks on the basis of combinatorial patterns of histone marks. By modeling the sparse distribution of histone marks with a zero-inflated Gaussian mixture, our partitions capture local BLOCKs that manifest relatively homogeneous enrichment pattern of histone marks. We further characterized BLOCKs by their transcription levels, distribution of genes, degree of co-regulation and GO enrichment. Our results demonstrate that these BLOCKs, although inferred merely from histone modifications, reveal strong relevance with physical domains, which suggests their important roles in chromatin organization and coordinated gene regulation.

KEYWORDS:

Bayesian change point model; Histone modification; chromosomal domain

PMID:
27231496
PMCID:
PMC4876974
[Available on 2017-03-01]
DOI:
10.1214/16-AOAS905
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