Charles David Allis

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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[edit]

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.


  • 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[edit]

Key Papers (selected from 310)[edit]

Histone acetylation/acetyltransferase-related[edit]

  • 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[edit]

  • 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)[edit]

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

  • 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[edit]

  • 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[edit]

  • 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. 



  • 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[edit]