RUNX1 contributes to higher-order chromatin organization and gene regulation in breast cancer cells

UMMS Affiliation

Department of Cell and Developmental Biology; Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology



Document Type



RUNX1 is a transcription factor functioning both as an oncogene and a tumor suppressor in breast cancer. RUNX1 alters chromatin structure in cooperation with chromatin modifier and remodeling enzymes. In this study, we examined the relationship between RUNX1-mediated transcription and genome organization. We characterized genome-wide RUNX1 localization and performed RNA-seq and Hi-C in RUNX1-depleted and control MCF-7 breast cancer cells. RNA-seq analysis showed that RUNX1 depletion led to up-regulation of genes associated with chromatin structure and down-regulation of genes related to extracellular matrix biology, as well as NEAT1 and MALAT1 lncRNAs. Our ChIP-Seq analysis supports a prominent role for RUNX1 in transcriptional activation. About 30% of all RUNX1 binding sites were intergenic, indicating diverse roles in promoter and enhancer regulation and suggesting additional functions for RUNX1. Hi-C analysis of RUNX1-depleted cells demonstrated that overall three-dimensional genome organization is largely intact, but indicated enhanced association of RUNX1 near Topologically Associating Domain (TAD) boundaries and alterations in long-range interactions. These results suggest an architectural role for RUNX1 in fine-tuning local interactions rather than in global organization. Our results provide novel insight into RUNX1-mediated perturbations of higher-order genome organization that are functionally linked with RUNX1-dependent compromised gene expression in breast cancer cells.

Rights and Permissions

Citation: Biochim Biophys Acta. 2016 Aug 9;1859(11):1389-1397. doi: 10.1016/j.bbagrm.2016.08.003. [Epub ahead of print] Link to article on publisher's site

Related Resources

Link to Article in PubMed


Breast cancer, Hi-C, MCF-7, RUNX1, TAD, Topologically associating domain

Journal Title

Biochimica et biophysica acta

PubMed ID