Identifying and characterizing transcriptional regulatory elements from chromosome conformation capture data

Abstract

Which features on the chromatin are responsible for regulating gene transcription? Using promoter contacts obtained from chromosome conformation capture (3C) data as a readout for transcriptional regulation, I modeled how well histone modification marks and chromatin accessibility predict promoter contact frequency. I found that promoter contacts were often located in the same topologically associating domain and that the correlation between promoter contact frequency and each chromatin feature varied across promoter gene expression level, with poised promoters less constrained than active or silent promoters when forming contacts. I applied this knowledge to understand the molecular changes that occurred at several limb development enhancers in a mouse selective breeding experiment for longer tibia called “Longshanks."