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.

Education[edit]

  • 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

Honors & Awards[edit]

  • 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-Leopold Mayer Prize
  • 2015 Breakthrough Prize in Life Sciences

Key Papers (selected from 310)[edit]

Histone acetylation/acetyltransferase-related[edit]

1. Brownell, J.E., Zhou, J., Ranalli, T., Kobayashi, R., Edmondson, D.G., Roth, S.Y. and Allis, C.D. (1996) Tetrahymena histone acetyltransferase A: A homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84, 843-851


2. Kuo, M.-H., Brownell, J.E., Sobel, R.E., Ranalli, T.A., Cook, R.G., Edmondson, D.G., Roth, S.Y. and Allis, C.D. (1996) Transcription-associated acetylation of histones H3 and H4 at specific lysines by Gcn5p. Nature 383, 269-272


3. Kuo, M.-H., Zhou, J., Jambeck, P., Churchill, M. and 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


Histone phosphorylation/kinase-related: disease links[edit]

1. Sassone-Corsi, P., Mizzen, C.M., Cheung, P., Crosio, C., Monaco, M., Jacquot, S., Hanauer, A. and Allis, C.D. (1999) Requirement of Rsk-2 for Epidermal Growth Factor-activated phosphorylation of histone H3. Science 285, 886-891


2.Wei, Y., Yu, L., Bowen, J., Gorovsky, M.A. and Allis, C.D. (1999) Phosphoryation of histone H3 is required for proper chromosome condensation and segregation. Cell 97, 99-109


3. Cheung, P., Tanner, K.G., Cheung, W.L., Sassone-Corsi, P., Denu, J.M. and Allis, C.D. (2000) Synergistic coupling of histone H3 phosphorylation and acetylation in response to mitogen stimulation. Mol. Cell 5, 905-915


4. Hsu, J.-Y., Sun, Z.-W., Li, X., Reuben, M., Tatchell, K., Bishop, D.K., Grushcow, Brame, C.J., Caldwell, J.A., Hunt, D.F., Lin, R., Smith, M.M. and 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


5. 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)


6. Ahn, S.-H., Cheung, W.L., Hsu, J.-Y., Smith, M.M. and Allis, C.D. (2005) Sterile 20 kinase phosphorylates histone H2B at serine10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell 120, 25-36


7. Ahn, S., Diaz, R.L., Grunstein, M. and 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


8. 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. and Allis, C.D. (2009) WSTF regulates the DNA damage response of H2A.X via a novel tyrosine kinase activity. Nature 457, 57-62


Histone code/theory-related (and extensions thereof)[edit]

1. Strahl, B.D. and Allis, C.D. (2000) The language of covalent histone modifications. Nature 403, 41-45


2. Jenuwein, T. and Allis, C.D. (2001) Translating the histone code. Science 293, 1074-1080


3. Fischle, W., Wang, Y. and Allis, C.D. (2003) Binary switches and modification cassettes in histone biology and beyond. Nature 425, 475-479


4. Ruthenburg, A.J., Li, H., Patel, D.J. and Allis, C.D. (2007) Multivalent engagement of chromatin modifications by linked binding modules. Nat. Rev. Mol. Cell Biol. 12, 983-994


5. 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


6.Allis, C.D. and Muir, T.W. (2011) Spreading chromatin into chemical biology. ChemBioChem. 12, 264-279


Histone methylation/methyltransferase-related[edit]

1. Rea, S., Eisenhaber, F., O'Carroll, D., Strahl, B., Sun-Zu-Wen, Schmid, M., Opravil, S., Mechtler, K., Pontig, C., Allis, C.D.* and Jenuwein, T.* (2000) Regulation of chromatin structure by site-specific histone methyltransferases. Nature 406, 593-599 (note * = co-corresponding authors)


2. Fischle, W., Tseng, B.S., Dormann, H., Ueberheide, B.M., Garcia, B.A., Shabanowitz, J., Hunt, D.F., Funabiki, H. and Allis, C.D. (2005) Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature 438, 1116-1122


3. Wysocka, J., Swigut, T., Xiao, H., Landry, J., Kauer, M., Tackett, A., Chait, B., Brivanlou, A.H., Wu, C. and 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


4. 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. and 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


5. Wang, G.W., Song, J., Wang, Z., Dormann, H., Casadio, F., Li, H., Patel, D. and Allis, C.D. (2009) Haematopietic malignancies initiated by dysregulation of an H3K4me3-engaging PHD finger. Nature 459, 847-851


6.Milne, T., Kim, J., Wang, G.G., Basrur, V., Whitcomb, S., Wang, Z., Ruthenburg, A., Elenitoba-Johnson, K., Roeder, R. and Allis, C.D. (2010) Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis. Mol. Cell 38, 853-863


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

1. 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


2. Elsaesser, S.J., Huang, H., Lewis, P.W., Chin, J.W., Allis, C.D.* and Patel, D.J.* (2012) Daxx envelops a histone H3.3-H4 dimer H3.3-specific recognition. Nature Oct 17. doi: 10.1038/nature11608. [Epub ahead of print] (note * = co-corresponding authors)


3. 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. and Allis, C.D. (2013) Inhibition of PRC2 activity by gain-of-function mutations found in pediatric glioblastoma. Science March 28 [Epub ahead of print]

Notes[edit]

  1. ^ Philippidis 2014

References[edit]

  • 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]