How Chromatin Conformation Impacts Gene Regulation In 3D The Genome

How Chromatin Conformation Impacts Gene Regulation In 3D The Genome ...

It becomes possible to identify long-range promoterenhancer interactions that might impact disease by mapping the genome structure in a three-dimensional (3D) format. This might be useful as a guideline to identifying new diagnostic biomarkers and approaches for developing therapeutics.

Dovetail Genomics develop assay kits that enable researchers to see the chromatin structure of human genomes in 3D. Technology Networks spoke with Dovetail Genomics CEO Todd Dickinson to discuss how Hi-C chromatin immunoprecipitation works and how it has been used in prostate cancer research.

Katie Brighton (KB): Could you describe the importance of genomics strategies in cancer research? What role is Dovetail Genomics in this space?

Cancer dysregulates gene transcriptional programs, leading to cell proliferation, immune surveillance evasion, and ultimately metastasis. Gene promoter interactions with regulatory elements, such as enhancers and silencers, are crucial to understanding cancer initiation and progression. This mechanism of enhancer hijacking has been linked to multiple cancers.

Increased proximity ligation gives researchers the potential to improve cancer progression by 3D mapping.

Proximity ligation kits, like Dovetail Genomics, enable researchers to see key 3D features of human disease, revealing currently unprobed dimensions that are contributing to oncogenic mechanisms and leading to a greater understanding of promoter activity. Only with this 3-d interaction between genes and regulatory elements can one completly power translational research.

Can you explain further how the Hi-C chromatin immunoprecipitation (HiChIP) technology works, and how it differs from other methods used to analyse the genome?

TD: HiChIP technology allows researchers to see ChIP-seq data in a whole new dimension. In the context of transcription factors and other chromatin modulators, this only partially captures their role and protein-mediated interactions with distal factors. HiChIP only provides a linear understanding and does not provide information to fully understand how protein-directed interactions are affected by protein interactions. These interactions may influence gene expression and promote disease progression.

KJ: A recent study revealed that inhibiting a chromatin remodeling complex prevented oncogene expression and cancer spread in prostate cancer patients. Could you clarify the role of HiChIP in this study?

TD: A proprietary proteolysis targeting chimera (PROTAC) medication used to promote prostate cancer is found in embryos, allowing for for the first time, to suppress oncogene expression, thus slowing prostate cancer growth in cells and animal studies. Dovetails'' HiChIP MNase kit provided valuable information on the 3D chromatin architecture, demonstrating the involvement of promoter hijacking by oncogenes that drive prostate cancer progression in disease samples and reversal of this mechanism in PRO

KB: Are there any other areas of research that might benefit from HiChIP technology, or are perhaps already benefiting?

TD: Due to the wide scope of the data available, there are many research areas that may benefit from HiChIP technology, including epigenetics, developmental biology, neurobiology, and oncology. The HiChIP proximity ligation technique focuses on long-range interactions using standard Illumina paired-end sequencing and helps researchers investigate how primary protein binding and protein-mediated chromatin interactions influence gene expression.

The Dovetail HiChIP MNase assay gives researchers new capabilities to discover enhancerpromoter interactions that control gene expression. These assays reveal where proteins lie and the long-range interactions they mediate. While it isn''t a complete replacement to ChIP-seq (ChIP-seq data is helpful in interpreting the more complex nature of HiChIP data), it adds a previously ignored dimension to ChIP-seq data by uncovering interactions.

Katie Brighton, a scientific copywriter for Technology Networks, spoke with Todd Dickinson.

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