Charles David Allis (born March 22, 1951) is an American molecular biologist, and is currently the Joy and Jack Fishman Professor and Head of the Laboratory of Chromatin Biology and Epigenetics at The Rockefeller University. In pursuit of understanding the DNA-histoneprotein complex and the intricate system which allows for gene activation, the Allis lab focuses on chromatin signaling via histone modifications - acetylation, methylation and phosphorylation. Allis is best known for deciphering regulatory mechanisms that impinge upon the fundamental repeating unit of chromatin and for identifying the responsible enzyme systems that govern the covalent modifications of histone proteins, the principal components that organize chromatin. Allis discovered the critical link, through histone acetyltransferase-containing transcriptional coactivators, between targeted histone acetylation and gene-specific transcriptional activation. In further studies, he linked histone phosphorylation events to mitosis and mitogen action, established a synergy between histone phosphorylation and acetylation events and elaborated the ‘histone code hypothesis’ (and extensions thereof), one of the most highly cited theories governing epigenetics. Implications of this research for human biology and human disease, notably cancer, are far-reaching and continuing at a remarkable pace.
Chromatin is the physiological template of our genome. The packaging of DNA within chromatin, the orderly replication and distribution of chromosomes, the maintenance of genome integrity, and the regulated expression of genes depend upon the highly conserved histone proteins. Despite a longstanding appreciation of the primary structure of histones, various covalent modifications, and speculation about regulatory roles for histones in gene expression, the field was plagued for many years because of poor methods for histone/chromatin isolation, consequent histone/chromatin aggregation, and lack of any clear distinction between a basic uniform (repeating) chromatin structure versus a more heterogeneous array of histone modifications along the genome. It was generally believed that histone proteins were passive participants in packaging DNA into a more manageable form. Before Allis’ work, it was not appreciated that histone proteins might play an active role in dictating meaningful biological responses. No histone-modifying activity was known; thus, there was no reason to anticipate that transcription machinery might possess histone-modifying enzymatic functions.
Indiana University, Ph.D., Biology, 1978, Public Health Service Pre-doctoral Fellow, thesis title: "Isolation and characterization of pole cells and polar granules from Drosophila melanogaster," Dr. Anthony Mahowald, thesis advisor
Kuo, M.-H.; Brownell, J.E.; Sobel, R.E.; Ranalli, T.A.; Cook, R.G.; Edmondson, D.G.; Roth, S.Y.; Allis, C.D. (1996). "Transcription-associated acetylation of histones H3 and H4 at specific lysines by Gcn5p". Nature383: 269–272. doi:10.1038/383269a0.
Kuo, M.-H.; Zhou, J.; Jambeck, P.; Churchill, M.; Allis, C.D. (1998). "Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo". Genes & Dev.12: 627–639. doi:10.1101/gad.12.5.627.
Sassone-Corsi, P.; Mizzen, C.M.; Cheung, P.; Crosio, C.; Monaco, M.; Jacquot, S.; Hanauer, A.; Allis, C.D. (1999). "Requirement of Rsk-2 for Epidermal Growth Factor-activated phosphorylation of histone H3". Science285: 886–891. doi:10.1126/science.285.5429.886.
Wei, Y.; Yu, L.; Bowen, J.; Gorovsky, M.A.; Allis, C.D. (1999). "Phosphoryation of histone H3 is required for proper chromosome condensation and segregation". Cell97: 99–109. doi:10.1016/s0092-8674(00)80718-7.
Cheung, P.; Tanner, K.G.; Cheung, W.L.; Sassone-Corsi, P.; Denu, J.M.; Allis, C.D. (2000). "Synergistic coupling of histone H3 phosphorylation and acetylation in response to mitogen stimulation". Mol. Cell5: 905–915. doi:10.1016/s1097-2765(00)80256-7.
Hsu, J.-Y.; Sun, Z.-W.; Li, X.; Reuben, M.; Tatchell, K.; Bishop, D.K.; Grushcow, Brame; Caldwell, J.A.; Hunt, D.F.; Lin, R.; Smith, M.M.; Allis, C.D. (2000). "Mitotic phosphorylation of histone H3 is governed by Ipl1p/aurora kinase and Glc7p/PP1 phosphatase in budding yeast and nematodes". Cell102: 279–291. doi:10.1016/s0092-8674(00)00034-9.
Cheung, W.L., Ajiro, K., Kloc, M., Cheung P., Mizzen, C.A., Beeser, A., Etkin, L.D., Chernoff, J. and Allis, C.D. (2003) Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase" Cell 16, 507-517 (featured article)
Ahn, S.-H.; Cheung, W.L.; Hsu, J.-Y.; Smith, M.M.; Allis, C.D. (2005). "Sterile 20 kinase phosphorylates histone H2B at serine10 during hydrogen peroxide-induced apoptosis in S. cerevisiae". Cell120: 25–36. doi:10.1016/j.cell.2004.11.016.
Ahn, S.; Diaz, R.L.; Grunstein, M.; Allis, C.D. (2006). "Histone H2B deacetylation at lysine 11 is required for yeast apoptosis induced by phosphorylation of H2B at serine 10. H2B". Mol. Cell24: 211–220. doi:10.1016/j.molcel.2006.09.008.
Xiao, A.; Li, H.; Shechter, D.; Ahn, S.H.; Fabrizio, L.A.; Erdjument-Bromage, H.; Murakami-Ishibe, S.; Wang, B.; Tempst, P.; Hofmann, K.; Patel, D.J.; Elledge, S.J.; Allis, C.D. (2009). "WSTF regulates the DNA damage response of H2A.X via a novel tyrosine kinase activity". Nature457: 57–62. doi:10.1038/nature07668.
Philippidis, Alex (2014). "Rockefeller Professor Wins Japan Prize". Gen. Eng. Biotechnol. News (paper) 34 (4): 7. ...for the pioneering work of his lab in discovering that chemical modifications of DNA-packaging proteins play a key role in regulating the activity of individual genes.