|CHANGE POINT ANALYSIS OF HISTONE MODIFICATIONS REVEALS EPIGENETIC BLOCKS LINKING TO PHYSICAL DOMAINS.
|Year of Publication
|Chen, Mengjie, Haifan Lin, and Hongyu Zhao
|Ann Appl Stat
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 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.
|Ann Appl Stat
|Change point analysis of histone modifications reveals epigenetic blocks linking to physical domains.
|PubMed Central ID
|P01 CA142538 / CA / NCI NIH HHS / United States
P30 CA016359 / CA / NCI NIH HHS / United States
R01 CA082659 / CA / NCI NIH HHS / United States