Cancer

Cancer involves the dysregulation of gene transcriptional programs that lead to sustained proliferation, immune surveillance evasion, and ultimately the promotion of metastasis. Mapping the dynamics of gene promoter interactions with their cognate regulatory elements, such as enhancers and silencers, is key to understanding the mechanistic drivers of cancer initiation and progression. This can lead to the identification of new biomarkers that will enable earlier diagnosis and usher in novel, untapped therapeutic treatments. However, limiting your studies to linear sequence when investigating proximal enhancer/silencer-promoter interactions only offers part of the story.

With proximity ligation, you can uncover the role that distal DNA regulatory mechanisms play in oncogenic programs. Chromatin loops and topologically associated domains (TADs) can, for example, tether enhancers up to a megabase or more away to oncogenic promoters to drive their expression. This enhancer “hijacking” has been tied to multiple cancer types.^1-3

With kits like the Dovetail^® Micro-C Kit and Dovetail Pan Promoter Enrichment Kits you’ll be able to:

• Reveal oncogenic mechanisms of action using a 3D view
• Discover regulatory elements modulating promoter activity
• Get a comprehensive view of protein binding & protein-mediated chromatin interactions without any bias due to restriction enzyme density
• Gather fine-scale, high-resolution topology mapping with an easy workflow that doesn’t require variable-introducing sonication

Linking Sequence Variation to Chromatin Dynamics through Genome Topology webinar

1. A High-Resolution 3D Epigenomic Map Reveals Insights into the Creation of the Prostate Cancer Transcriptome. Rhie SK, et al., Nat. Commun., 2019.
2. Epigenetic Reprogramming at Estrogen-Receptor Binding Sites Alters 3D Chromatin Landscape in Endocrine-Resistant Breast Cancer. Achinger-Kawecka J, et al., Nat. Commun., 2020.
3. Genome-Wide Analysis of Therapeutic Response Uncovers Molecular Pathways Governing Tamoxifen Resistance in ER+ Breast Cancer. Rahem SM, et al., The Lancet, 2020.