کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1946277 | 1400352 | 2016 | 9 صفحه PDF | دانلود رایگان |

• RUNX1 depletion leads to dysregulation of genes associated with chromatin structure and extracellular matrix biology.
• RUNX1 binds similarly to promoters, introns, and intergenic regions, indicating diverse roles in gene and enhancer regulation.
• RUNX1 binds similarly to genic and intergenic regions, indicating diverse roles in gene and enhancer regulation.
• Hi-C analysis identifies RUNX1 as a contributor of local chromatin interactions, rather than a global genome organizer.
• This study provides an overview of the role of RUNX1 in gene expression and genome structure in breast cancer cells.
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.
Journal: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms - Volume 1859, Issue 11, November 2016, Pages 1389–1397