[CCoE Notice] Seminar: Application of protein microarrays in analyzing methylated DNA-protein interactions in humans

[Grayson, Audrey A]

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Seminar
Application of protein microarrays in analyzing methylated DNA-protein interactions in humans
Hu S, Wan J, Su Y, Song Q, Zeng Y, Nguyen HN, Shin J, Cox E, Rho HS, Woodard C, Xia S, Liu S, Lyu H, Ming GL, Wade H, Song H, Qian J, Zhu H.
Friday, April 8, 2016
SEC 204: 12:00 PM – 1:00 PM
Speaker: Dr. Heng Zhu

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Abstract: Fueled by the fast-growing genomics information, the next challenge is to characterize protein functionality and understand how cell functions on the systems level.  Protein microarrays, especially functional protein microarrays, have become a powerful and versatile tool for proteomics studies. In this seminar, I will first describe the recent technology development in protein microarrays. To illustrate the power of this technology, I will report one of our recent projects to better understand the molecular principle of epigenetic regulation. We used a protein microarray-based approach to systematically survey the entire human TF family and found numerous purified TFs with methylated CpG (mCpG)-dependent DNA-binding activities. Interestingly, some TFs exhibit specific binding activity to methylated and unmethylated DNA motifs of distinct sequences. To elucidate the underlying mechanism, we focused on Kruppel-like factor 4 (KLF4), and decoupled its mCpG- and CpG-binding activities via site-directed mutagenesis. Furthermore, KLF4 binds specific methylated or unmethylated motifs in human embryonic stem cells in vivo. Finally, in-depth in vivo analysis identified a novel mechanism by which mCpG-dependent binding activity of KLF4 recognizes and activate transcription of genes in closed chromatins. Our study suggests that mCpG-dependent TF binding activity is a widespread phenomenon and provides a new framework to understand the role and mechanism of TFs in epigenetic regulation of gene transcription.

Bio: Heng Zhu,PhD is a Full Professor at Department of Pharmacology and Molecular Sciences at Johns Hopkins University School of medicine. He also holds appointments in the High-Throughput Biology Center and the Oncology Department at Hopkins. Dr. Zhu received his B.S. degree at Peking University, China and obtained his Ph.D. degree in Genetics (Dr. Ralph Dean) at Clemson University, South Carolina.  Dr. Zhu did his postdoctoral research in Dr. Michael Snyder's group at Yale University when he and his colleagues invented the proteome chip technology. In 2004, Dr. Zhu joined the faculty of the Johns Hopkins University School of Medicine. During the years, Dr. Zhu’s group has been focusing on the development and application of proteome microarrays to address both basic and clinical questions. His group has constructed the world-largest proteome microarray, comprised of ~20,000 individually purified human proteins in full-length. Using this powerful tool, his group has developed new approaches to identify substrates of various types of protein modification enzymes, such as kinases, acetyltransferases, ubiquitin and SUMO E3 ligases, and to construct signaling networks and pathways. His group has also applied the human proteome microarrays to determine the underlining principle of pathogen-host interactions. In parallel, Dr. Zhu and colleagues applied the human proteome microarrays to discovery novel biomarkers in autoimmune diseases and cancer.

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