I. Epigenetics: Why Your DNA Isn’t Enough
II. Epigenetics in Development and Disease
Part I: Epigenetics: Why Your DNA Isn’t Enough
|Download: High Res Low ResSubtitled Videos: English|
|Resources: Transcript (.txt)(.xls)|
|Resources: Related ArticlesRecorded: 2016|
|Trouble Viewing? Try it on iTunes.Report a problem.|
In the first of his videos, Dr. Allis introduces the concept of epigenetics; a change in a cellular phenotype that is not due to DNA mutation but due to chemical modifications of proteins that result in changes in gene activation. In the nucleus, DNA is wrapped around proteins called histones to form chromatin. How tightly the chromatin is packaged determines whether genes are active or not. This switch between the “on and off” state of chromatin is regulated by chemical modification of histones. Allis describes work from his lab and others that identified the enzymes that add, remove and recognize the histone modifications. Changes in histone modification can cause a number of diseases including cancer. A key difference between genetic mutations and epigenetic modifications is that epigenetic changes are reversible making them an attractive drug target.
Dr. Allis focuses on the role of epigenetics in development and disease in his second talk. Histones can be modified on a number of amino acids, particularly lysines, by the addition of acetyl or methyl groups. Combinatorial patterns of these modifications act to enhance or repress gene expression. Allis describes work from his lab and others, which demonstrates that mutations in histone (for instance a lysine to methionine mutation) may block these modifications and, thus, impact gene expression. Sadly, these “onco-histone” mutations have been identified as the cause of many diseases including pediatric brain tumors and pancreatic neuroendocrine tumors.
David Allis is the Joy and Jack Fishman Professor and Head of the Laboratory of Chromatin Biology and Epigenetics at The Rockefeller University. Allis’ lab studies how modifications to histones, the proteins that package DNA, influence gene expression and the implications these changes have for human disease.
Allis has been honored with many awards for his pioneering research including the 2015 Breakthrough Prize in Life Sciences, the 2014 Japan Prize, the 2007 Canada Gairdner International Award and many others. Allis is a member of the National Academy of Sciences USA, the American Academy of Arts and Sciences and the French Academy of Sciences.
Allis received his BS in biology from the University of Cincinnati and his PhD in biology from Indiana University and he was a post-doctoral fellow at the University of Rochester.
- J. Michael Bishop iBioSeminar: Cancer: The Rise of the Genetic Paradigm
- Susan Lindquist iBioSeminar: Protein Folding, Prions and Disease
- Alfredo Quiñones- Hinojosa iBioSeminar: Brain Tumors and Stem Cells
- Robert Tjian iBioSeminar: The Molecular Biology of Gene Regulation
Lewis, P.W., Mueller, M.M., Koletsky, M.S., Cordero, F., Lin, S., Banaszynski, L.A., Garcia, B.A., Muir, T.W., Becher, O.J. and Allis C.D. (2013) Inhibition of PRC2 activity by gain-of-function mutations in pediatric glioblastoma. Science 340, 857-861
Maze, I., Noh, K.M. and Allis, C.D. (2014) Every amino acid matters: essential contributions of histone variants to mammalian development and disease. Nature Rev. Genetics, 15, 259-271
Allis, C.D. (2015) “Modifying” my career toward chromatin biology. J. Biol. Chem. 290, 15904-15908
Lu, C., Jian, S.U., Hoelper, D., Bechet, D., Molden, R.C., Ran, L., Murphy, D., Venneti, S., Hameed, M., Pawel, B.R., Wunder, J., Dickson, B.C., Sawyer, S.L, Grynspan, D., Nadaf, J., Fahiminiyah, S., Majewski, J., Thompson, C.B., Chi, P., Garcia, B.A., Allis, C.D., Jabado, N. and Lewis, P.W. (2016) Histone H3K36 mutations impair mesenchymal differentiation and drive sarcoma development. Science, in press