The Genome in 3D How Chromatin Conformation Begins Gene Regulation

The Genome in 3D How Chromatin Conformation Begins Gene Regulation ...

It becomes possible to demonstrate long-range promoterenhancer interactions that might impact the disease, by mapping the genome structure in a three-dimensional (3D) format. It is possible to identify new diagnostic biomarkers and strategies for developing therapeutics.

Katie Brighton (KB): Could you discuss the importance of genomics approaches in cancer research? What role does Dovetail Genomics play 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 numerous cancers.

These enhancerpromoter interactions can not only help elucidate the mechanism of disease, but also identify new biomarkers, which may enable earlier diagnosis and ushering in therapeutic therapies. Ultimately, with proximity ligation, researchers can better understand the role these distal DNA regulatory mechanisms play in oncogenic progression.

Proximity ligation kits, like those offered by Dovetail Genomics, enable researchers to see key 3D features of human disease, revealing previously unprobed dimensions, leading to oncogenic mechanisms, and enabling a greater understanding of how regulatory elements affect promoter activity. Only with the addition of this 3D interaction between genes and regulatory elements, one can fully assist translational research.

Could you explain more about the Hi-C chromatin immunoprecipitation (HiChIP) technology and how it works, and how it compares to other methods used to analyze the genome?

TD: HiChIP technology allows researchers to see ChIP-seq data in a completely new way. However, this only partially captures their role as ChIP-seq, as well as protein-directed interactions. Unlike other chromatin modules, HiChIP only discloses contact information that is identified as regulatory elements and gene promoters. These include interactions that can affect gene expression and drive disease progression.

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

TD: A study commissioned by University of Michigan researchers found that a proprietary proteolysis targeting chimera (PROTAC) drug aimed at the SWI/SNF chromatin remodeling complex was used for the first time in cell and animal experiments. Dovetails'' proximity-ligation technology enabled significant advances in prostate cancer development.

Is there any other research opportunity that might benefit from HiChIP technology, or is it already benefiting?

TD: Due to the depth of the data generated, there are a number of research areas that may benefit from HiChIP technology, including epigenetics, developmental biology, neurobiology, and oncology. To understand the mechanisms of gene regulation, the protein factors must be studied in their native 3D environment. The HiChIP proximity ligation technique uses standard Illumina paired-end sequencing to investigate primary protein binding and protein-mediated chromatin interactions.

The Dovetail HiChIP MNase experiment gives researchers new tools to investigate enhancerpromoter interactions that influence gene expression. These assays help to understand where proteins bind and the long-range interactions they involve. Although the Dovetail HiChIP MNase research isn''t a complete replacement to ChIP-seq (ChIP-seq data is helpful in translating the more complex nature of HiChIP data), it adds a currently ignored dimension to ChIP-seq data by discovering

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