Identification of recurrent combinatorial patterns of chromatin modifications at promoters across various tissue types

Abstract

Background: Identification and analysis of recurrent combinatorial patterns of multiple chromatin modifications provide invaluable information for understanding epigenetic regulations. Furthermore, as more data becomes available, it is computationally expensive and unnecessary to study combinatorial patterns of all modifications. Methods: A novel framework is proposed to investigate recurrent combinatorial patterns of a subset of quantitatively selected chromatin modifications. The framework is based on heirarchical clustering and selects subsets of chromatin modifications that form distinct recurrent patterns at regulatory regions. The identified recurrent combinatorial patterns can be further utilized to discover novel regulatory regions. Data is in the form of genome wide maps of histone acetylations, methylations, and histone variant of human skeletal muscular and B-lymphocyte cells both derived from the ENCODE project. Results: A case study conducted at promoter regions is presented: four out of twelve chromatin modifications were selected, eight different promoter states were identified and the identified patterns of active promoters were further utilized to discover novel promoter regions. Several previously un-annotated promoters were discovered, further investigations confirm their promoter functions. Conclusions: This framework is approproiately general and could lead to better understanding of epigenetic regulations by discovering previously unknown regulatory regions.