Abstract 5370: Examination of DNA looping near oncogenes reveals variable patterns of epigenetic landscapes in cancer

Abstract

Abstract INTRODUCTION: The compaction of chromatin in the nucleus into hierarchical three-dimensional (3D) structures plays a key role in the regulation of gene expression. Advancements in high-throughput chromatin conformation capture assays have enabled the determination of this hierarchical structure in a variety of cell states, including cancer. Of note, recent studies have implicated pathogenic alterations in 3D topology of the genome with the activation of proto-oncogenes in a multitude of cancers. METHODS: To characterize the topological changes associated with different cancer phenotypes, we examine publically available epigenetic profiles from the ENCODE Project, including 3D data from Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET) from breast cancer and leukemia cell lines. Integrating the chromatin topology data with transcription factor binding, DNase accessibility, and histone modification data, we uncover variable epigenetic landscapes associated with differentially active oncogenes in these cancer cell lines. RESULTS: We provide evidence of topological variability influencing differentially expressed oncogenes and tie these observations to other epigenetic changes. In particular, we show insulated-neighborhoods mediated by CTCF looping partition segments of the genome containing active oncogenes away from repressive markings like H3K4me3. Additionally, we show that variation in topology differentially localizes H3K27ac in distal regulatory regions to promoters of oncogenes, providing a means for gene activation in non-coding regions. CONCLUSIONS: Variable patterns of chromatin topology provide a unique signature and mechanism of oncogenes for cancerous phenotypes. We use publically available data to show mechanisms of activity associated with chromatin topology variation. Citation Format: Monika Perez, Ty Johannes. Examination of DNA looping near oncogenes reveals variable patterns of epigenetic landscapes in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5370. doi:10.1158/1538-7445.AM2017-5370