Charles David Allis

C. David Allis

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-histone protein 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.

Research Significance

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.

Education

• University of Cincinnati, B.S., summa cum laude, Biology, 1973
• 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
• University of Rochester, Biology, 1978-1981, National Institutes of Health Postdoctoral fellow, area of study: Cellular and Molecular Biology, Dr. Martin Gorovsky, postdoctoral advisor

Honors & Awards

• B.S., summa cum laude
• Phi Beta Kappa
• 2001: Election to the American Academy of Arts and Sciences
• 2001: DeWitt Stetten Jr. Award Recipient, sponsored by the Institute of General Medical Sciences, NIH
• 2002: Dickson Prize in Medicine at the University of Pittsburgh School of Medicine
• 2003: Massry Prize in Chromatin and Transcription (shared with Drs. Michael Grunstein and Roger Kornberg)
• 2004: Wiley Prize for Distinguished Research in the Biomedical Sciences
• 2005: Elected to the National Academy of Sciences,
• 2007: Distinguished Alumnus Award, University of Cincinnati
• 2007: Gairdner Foundation International Award
• 2008: ASBMB-Merck Award for Distinguished Research in the Biomedical Sciences
• 2011: Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research (shared with Dr. Michael Grunstein), Brandeis University
• 2011: Howard T. Ricketts Prize for Distinguished Research in the Biomedical Sciences, University of Chicago
• 2013: Nicholson Award Lecturer at the Karolinska Institutet, Stockholm, Sweden
• 2014: Japan Prize^[1]
• 2014: Charles-Léopold Mayer Prize of the Académie des Sciences, France
• 2015: Breakthrough Prize in Life Sciences

Key Papers (selected from 310)

Histone acetylation/acetyltransferase-related

• Brownell, J.E.; Zhou, J.; Ranalli, T.; Kobayashi, R.; Edmondson, D.G.; Roth, S.Y.; Allis, C.D. (1996). "Tetrahymena histone acetyltransferase A: A homolog to yeast Gcn5p linking histone acetylation to gene activation". Cell 84: 843–851. doi:10.1016/s0092-8674(00)81063-6.
• 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". Nature 383: 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.

Histone phosphorylation/kinase-related: disease links

• 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". Science 285: 886–891. doi:10.1126/science.285.5429.886. PMID 10436156.
• 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". Cell 97: 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. Cell 5: 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". Cell 102: 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". Cell 120: 25–36. doi:10.1016/j.cell.2004.11.016. PMID 15652479.
• 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. Cell 24: 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". Nature 457: 57–62. doi:10.1038/nature07668.

Histone code/theory-related (and extensions thereof)

• Strahl, B.D.; Allis, C.D. (2000). "The language of covalent histone modifications". Nature 403: 41–45. doi:10.1038/47412. PMID 10638745.

• Jenuwein, T.; Allis, C.D. (2001). "Translating the histone code". Science 293: 1074–1080. doi:10.1126/science.1063127. PMID 11498575.

• Fischle, W.; Wang, Y.; Allis, C.D. (2003). "Binary switches and modification cassettes in histone biology and beyond". Nature 425: 475–479. doi:10.1038/nature02017.

• Ruthenburg, A.J.; Li, H.; Patel, D.J.; Allis, C.D. (2007). "Multivalent engagement of chromatin modifications by linked binding modules". Nat. Rev. Mol. Cell Biol 12: 983–994. doi:10.1038/nrm2298.
• Allis, C.D., Jenuwein, T., Reinberg, D. (eds.) and Caparros, M.L. (assoc. ed.) Epigenetics. Cold Spring Harbor laboratory Press. Cold Spring Harbor, NY, 2006
• Allis, C.D.; Muir, T.W. (2011). "Spreading chromatin into chemical biology". ChemBioChem. 12: 264–279. doi:10.1002/cbic.201000761.

Histone methylation/methyltransferase-related

• Rea, S.; Eisenhaber, F.; O'Carroll, D.; Strahl, B.; Sun-Zu-Wen, Schmid; Opravil, S.; Mechtler, K.; Pontig, C.; Allis, C.D.; Jenuwein, T. (2000). "Regulation of chromatin structure by site-specific histone methyltransferases". Nature 406: 593–599.
• Fischle, W.; Tseng, B.S.; Dormann, H.; Ueberheide, B.M.; Garcia, B.A.; Shabanowitz, J.; Hunt, D.F.; Funabiki, H.; Allis, C.D. (2005). "Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation". Nature 438: 1116–1122. doi:10.1038/nature04219. PMID 16222246.
• Wysocka, J.; Swigut, T.; Xiao, H.; Landry, J.; Kauer, M.; Tackett, A.; Chait, B.; Brivanlou, A.H.; Wu, C.; Allis, C.D. (2006). "A PHD finger in the largest subunit of NURF couples histone H3 K4 trimethylation with chromatin remodeling". Nature 442: 86–90. doi:10.1038/nature04815. PMID 16728976.

• Taverna, S.D.; Ilin, S.; Rogers, R.S.; Tanny, J.C.; Lavender, H.; Li, H.; Baker, L.; Boyle, J.; Blair, L.P.; Chait, B.T.; Patel, D.J.; Aitchison, J.D.; Tackett, A.J.; Allis, C.D. (2006). "Yng1 PHD finger binding to histone H3 trimethylated at lysine 4 targets lysine 14 specific NuA3 HAT activity to a subset of promoters for transcriptional activation". Mol. Cell 24: 1–12. doi:10.1016/j.molcel.2006.10.026.

• Wang, G.W.; Song, J.; Wang, Z.; Dormann, H.; Casadio, F.; Li, H.; Patel, D.; Allis, C.D. (2009). "Haematopietic malignancies initiated by dysregulation of an H3K4me3-engaging PHD finger". Nature 459: 847–851. doi:10.1038/nature08036.

• Milne, T.; Kim, J.; Wang, G.G.; Basrur, V.; Whitcomb, S.; Wang, Z.; Ruthenburg, A.; Elenitoba-Johnson, K.; Roeder, R.; Allis, C.D. (2010). "Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis". Mol. Cell 38: 853–863. doi:10.1016/j.molcel.2010.05.011.

Histone variant (H3.3) related with human disease links

• Goldberg, A.D.; Banaszynski, L.A.; Noh, K.M.; Lewis, P.W.; Elsaesser, S.J.; Stadler, S.; Dewell, S.; Law, M.; Guo, X.; Li, X.; Wen, D.; Chapgier, A.; DeKelver, R.C.; Miller, J.C.; Lee, Y.L.; Boydston, E.A.; Holmes, M.C.; Gregory, P.D.; Greally, J.M.; Rafii, S.; Yang, C.; Scambler, P.J.; Garrick, D.; Gibbons, R.J.; Higgs, D.R.; Cristea, I.M.; Urnov, F.D.; Zheng, D.; Allis, C.D. (2010). "Distinct factors control histone variant H3.3 localization at specific genomic regions". Cell 140: 678–691. doi:10.1016/j.cell.2010.01.003. PMC 2885838. PMID 20211137.
• Elsaesser, S.J.; Huang, H.; Lewis, P.W.; Chin, J.W.; Allis, C.D.; Patel, D.J. (2012). "Daxx envelops a histone H3.3-H4 dimer H3.3-specific recognition". Nature 491: 560–565. doi:10.1038/nature11608.

• Lewis, P.W.; Muller, M.M.; Koletsky, M.S.; Cordero, F.; Lin, S.; Banaszynski, L.A.; Garcia, B.A.; Muir, T.W.; Becher, O.J.; Allis, C.D. (2013). "Inhibition of PRC2 activity by gain-of-function mutations found in pediatric glioblastoma". Science 340: 857–861. doi:10.1126/science.1232245.

Notes

1. Philippidis 2014

References

• 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.

External links

• Allis Lab at The Rockefeller University
• National Academy of Sciences Profile of C. David Allis
• ISI Highly Cited Researchers