Research Report 2019_20

Richard M. Myers, PhD / Myers Lab

Gene expression and the human brain

identity and precise location of many functional elements in the human genome, such as non-protein encoding genes, promoters, and transcriptional regula- tory sequences, remain to be fully elucidated. The Ency- clopedia of DNA Elements (ENCODE) Project began af- ter the Human Genome Project with the goal of building a comprehensive list of functional elements in the hu- man genome. Myers’ lab has been major contributors to the ENCODE Project. At HudsonAlpha, his group collab- orates with HudsonAlpha Adjunct Faculty member Eric Mendenhall, PhD and his lab to generate large amounts of data that help explain how human genes are regulated. For the third phase of the ENCODE Project, Myers’ lab studied transcription factor biology in genome-wide experiments to expand the knowledge of DNA elements in both human and mouse genomes 1 . The project, over- seen by project manager Mark Mackiewicz, PhD and Chris Partridge, PhD, studied about a quarter of all of the expressed transcription factors in a human liver cancer cell line. It was the largest study of transcription factors expressed at physiological, or normal, levels to date. The researchers identified novel associations be- tween transcription factors, elaborated on their spatial interactions on DNA, and distinguished between those that interact with promoters and those that interact with enhancers in the genome. With the help of Mendenhall’s lab, this study continues to grow, more than doubling the number of transcription factors and adding additional functional data.

Although all of an individual’s cells contain the same DNA, each cell can become specific for a certain tis- sue or organ system by turning the expression of dif- ferent genes on and off. Gene expression is regulated by the binding of transcription factor proteins to short stretches of DNA, called regulatory elements, that serve as on/off switches for that gene. The regulation of gene expression controls the timing, location, and amount of gene products in a cell. This allows for the differen- tiation and development of unique cell types through- out the body, but can also lead to disease states if it becomes dysregulated.

Richard M. Myers, PhD in the lab

HudsonAlpha Faculty Investigator Richard M. Myers, PhD, and his lab study the human genome with the goal of understanding how changes in gene expres- sion contribute to human health and disease, as well as to basic biological processes. Myers’ group develops and applies innovative technologies and high-through- put next-generation sequencing technology to identify, characterize and understand gene regulatory systems. By first understanding gene expression and regulatory systems in a healthy state, his group then studies how they are altered during the development and progres- sion of human disease. Although a near-complete human genome se- quence was finished in 2003, with contributions from the genome center Myers directed at Stanford, the

Mark Mackiewicz, PhD studying transcription factors


HudsonAlpha Institute for Biotechnology

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