Exploring the genome-wide roles of transcription factors and their complexes in chromosome interaction

Abstract

The tight regulation of genes in different cells is governed by temporal and spatial biological signals. It is very important to pinpoint the pattern of transcription factors (TFs) and their complexes in looping interactions and to detect TF complexes as well as the underlying cis-regulatory modules (CRMs) in different human cell types. Existing studies on analysis of TFs and their complexes were only performed at one dimension and not at genome-wide scale. Recently, the unbiased chromosome conformation capture, Hi-C, can detect the genome-wide chromatin interactions, but has restrictions on its resolution due to the variable cell-to-cell chromosome structures and inadequate sequencing depth. In this study, we provide a comprehensive analysis on TFs regulatory pattern within chromosome looping by combining Hi-C and ENCODE ChIP-Seq data from three human cell types (GM12878, H1-hESC and K562). We first devised a strategy to map ChIP-Seq peaks of each TF to a normalized 10kb Hi-C contact matrix and construct an interaction matrix for each participant TF. We observed tight correlation for TFs participant activities in high resolution chromosome looping between biological replicates, which indicate the TF activities is more stable than local DNA interactions. To check the enrichment of different chromatin marks and genomic features in the interaction region of each participant TF, we performed enrichment test on ...