Uncovering direct and indirect molecular determinants of chromatin loops using a computational integrative approach.

ABSTRACT: Chromosomal organization in 3D plays a central role in regulating cell-type specific transcriptional and DNA replication timing programs. Yet it remains unclear to what extent the resulting long-range contacts depend on specific molecular drivers. Here we propose a model that comprehensively assesses the influence on contacts of DNA-binding proteins, cis-regulatory elements and DNA consensus motifs. Using real data, we validate a large number of predictions for long-range contacts involving known architectural proteins and DNA motifs. Our model outperforms existing approaches including enrichment test, random forests and correlation, and it uncovers numerous novel long-range contacts in Drosophila and human. The model uncovers the orientation-dependent specificity for long-range contacts b

SUBMITTER: Mourad R 

PROVIDER: S-EPMC5462476 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature