Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers

TitleEnhancer networks revealed by correlated DNAse hypersensitivity states of enhancers
Publication TypeJournal Articles
Year of Publication2013
AuthorsMalin J., Aniba M.R, Hannenhalli S
JournalNucleic Acids ResNucleic Acids ResNucleic Acids Res
Date PublishedAug
ISBN Number1362-4962 (Electronic)<br/>0305-1048 (Linking)
Accession Number23700312
Keywords*Deoxyribonucleases, *Enhancer Elements, Genetic, Chromatin/chemistry, Gene expression, Gene Regulatory Networks, HUMANS, Transcription Factors/metabolism

Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using approximately 100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity. We found widespread correlated activity between enhancers, which decreases with increasing inter-enhancer genomic distance. We found that correlated enhancers tend to share common transcription factor (TF) binding motifs, and several chromatin modification enzymes preferentially interact with these TFs. Presence of shared motifs in enhancer pairs can predict correlated activity with 73% accuracy. Also, genes near correlated enhancers exhibit correlated expression and share common function. Correlated enhancers tend to be spatially proximal. Interestingly, weak enhancers tend to correlate with significantly greater numbers of other enhancers relative to strong enhancers. Furthermore, strong/weak enhancers preferentially correlate with strong/weak enhancers, respectively. We constructed enhancer networks based on shared motif and correlated activity and show significant functional enrichment in their putative target gene clusters. Overall, our analyses show extensive correlated activity among enhancers and reveal clusters of enhancers whose activities are coordinately regulated by multiple potential mechanisms involving shared TF binding, chromatin modifying enzymes and 3D chromatin structure, which ultimately co-regulate functionally linked genes.

Short TitleNucleic acids researchNucleic acids research
Alternate JournalNucleic acids research