HudsonAlpha Research Report 2023-2024

Tess Vessels, PhD, Marshae Scott, and Jacob Loupe, PhD, looking at transcription factor expression data.

reveals how proteins interact with DNA. By leveraging the vast amount of ENCODE ChIP-seq data, Myers and his team found that most known candidate CREs are bound by at least one of the 680 assayed DNA-associated proteins, suggesting that this research has identified a significant portion of the regulatory elements in the human genome. The study not only confirmed the binding of many known transcription factors to their target genes but also uncovered novel transcription fac- tors and regulatory relationships. These findings provide valuable insights into the complex net- work of gene regulation in human cells and may have significant implications for understanding human disease and developing targeted thera- pies. The work highlights the enduring impact of the ENCODE Project and sets the stage for future discoveries in the field of gene regulation. While large-scale datasets like ENCODE have provided valuable insights into gene regulation, their reliance on cancer-derived cell lines of- ten limits their ability to accurately capture the complexities of gene expression in diverse human tissues, particularly the brain. In early 2024, Myers and his lab made a significant contribu- tion to the field of neuroscience by publishing

BrainTF , a comprehensive resource that maps the binding sites of more than 100 transcription factors in human postmortem brain tissue 2 . The study represents the largest dataset to date on transcription factor binding in human neurolog- ical cells, offering unprecedented insights into the intricate regulatory mechanisms governing gene expression in the brain. This brain study identified many novel transcription factor binding sites not found in existing databases, highlighting the unique aspects of brain regulation. The valuable data generated from this study is publicly available. By providing open access to this comprehensive resource from difficult-to-obtain brain tissues, the researchers aim to empower the scientific community to delve deeper into the intricate mechanisms of brain function and dysfunction, ultimately accelerating the development of novel therapeutic strategies for psychiatric illness- es. Further experiments are being done in the Myers Lab to understand the regulation of genes that cause neurodegenerative diseases and include ways of possibly mitigating the effects of these mutant genes. ■

Read this Everyday DNA blog article to learn more.

RESEARCH REPORT 2023-2024

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