Change point analysis of histone modifications reveals epigenetic blocks with distinct regulatory activity and biological functions
Mengjie Chen, Haifan Lin, Hongyu Zhao
(Submitted on 20 Sep 2013)

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 across the chromosome with a zero-inflated Gaussian mixture, our partitions capture local BLOCKs manifest relatively homogeneous enrichment pattern of histone modifications. We further characterized BLOCKs by their transcription levels, distribution of genes, binding profiles of a broad panel of chromatin proteins, degree of co-expression and GO enrichment. Our results demonstrate that these blocks, although inferred merely from histone modifications, reveal strong relevance with transcription events and chromatin organization, which suggest their important roles in coordinated gene regulation.