For the first time, scientists have tracked the activity, across the lifespan, of an environmentally responsive regulatory mechanism that turns genes on and off in the brain’s executive hub. Among key findings of the study by National Institutes of Health scientists: genes implicated in schizophrenia and autism turn out to be members of a select club of genes in which regulatory activity peaks during an environmentally-sensitive critical period in development. The mechanism, called DNA methylation, abruptly switches from off to on within the human brain’s prefrontal cortex during this pivotal transition from fetal to postnatal life. As methylation increases, gene expression slows down after birth.
Friday Lecture Series
Richard M. Furlaud Distinguished Lecture
X-Chromosome Inactivation as a Model for Epigenomic Regulation by Long
Jeannie T. Lee, M.D., Ph.D., professor of genetics and pathology,
Harvard Medical School, investigator,
Howard Hughes Medical Institute
January 27, 2012
3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)
Lengner, C. J., A. A. Gimelbrant, J. A. Erwin, A. W. Cheng, M. G. Guenther, G. G. Welstead, R. Alagappan, et al. 2010. Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell 141, (5): 872-883
Namekawa, S. H., B. Payer, K. D. Huynh, R. Jaenisch, and J. T. Lee. 2010. Two-step imprinted X inactivation: Repeat versus genic silencing in the mouse. Molecular and cellular biology 30, (13): 3187-3205
Sarma, K., P. Levasseur, A. Aristarkhov, and J. T. Lee. 2010. Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of xist RNA localization to the X chromosome. Proceedings of the National Academy of Sciences of the United States of America 107, (51): 22196-22201
Tian, D., S. Sun, and J. T. Lee. 2010. The long noncoding RNA, jpx, is a molecular switch for X chromosome inactivation. Cell 143, (3): 390-403
Zhou, D., C. Conrad, F. Xia, J. -S Park, B. Payer, Y. Yin, G. Y. Lauwers, et al. 2009. Mst1 and Mst2 maintain hepatocyte quiescence and Suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell 16, (5): 425-438
Discovering the step-by-step details of the path embryonic cells take to develop into their final tissue type is the clinical goal of many stem cell biologists. To that end, Kenneth S. Zaret, PhD, professor of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania, and associate director of the Penn Institute for Regenerative Medicine, and Cheng-Ran Xu, PhD, a postdoctoral researcher in the Zaret laboratory, looked at immature cells called progenitors and found a way to potentially predict their fate. They base this on how histones are marked by other proteins. Read about this research in the May 20, 2011 issue of SCIENCE.
Scientists at the Centre for Addiction and Mental Health (CAMH) have found evidence that a secondary molecular mechanism called epigenetics may also account for some inherited traits and diseases. Epigenetic factors may help explain currently unclear issues in human disease, such as the presence of a disease in only one monozygotic twin, the different susceptibility of males (e.g. to autism) and females (e.g. to lupus), significant fluctuations in the course of a disease (e.g. bipolar disorder, inflammatory bowel disease, multiple sclerosis), among numerous others. These factors represent a new way to look for the molecular cause of disease, and eventually may lead to improved diagnostics and treatment. See the research reported in Nature Genetics advance online publication January 2009.