In a multi-cellular organism, the genome in different cells is nearly identical, but each cell type has its own gene expression pattern and biological function. The variation of chromatin states plays an important role in regulating cell-type specific gene expression activities. Genome-wide chromatin state analyses have identified a large number of putative enhancer elements that are associated with distinct chromatin marks; however, it remains a challenge to distinguish functional elements from spurious ones, especially where multiple enhancer elements are adjacent to each other forming dense clusters. Recent studies suggest that these enhancer clusters are hotspots for functional elements that play important roles in maintenance of cell-identity and regulating cell-type specific gene expression patterns; however, the underlying mechanism remains unclear. Our recent experimental work strongly suggests that enhancer clusters are composed of a functional hierarchy of interdependent constituent elements. In this project, we will develop computational methods to predict and experimentally validate the enhancer hierarchy within super-enhancers, integrating information from Hi-C, ChIPseq, and RNAseq datasets. Our proposed research will provide powerful computational tools that will facilitate functional characterization of noncoding DNA.
Enhancer elements play an important role in gene regulation in development and diseases. Elucidating the functionality of enhancer elements will provide important insights into the biological functions of noncoding DNA sequences and the molecular mechanisms underlying human diseases.
|Pinello, Luca; Farouni, Rick; Yuan, Guo-Cheng (2018) Haystack: systematic analysis of the variation of epigenetic states and cell-type specific regulatory elements. Bioinformatics 34:1930-1933|
|Huang, Jialiang; Li, Kailong; Cai, Wenqing et al. (2018) Dissecting super-enhancer hierarchy based on chromatin interactions. Nat Commun 9:943|