John M. Denu Professor

University of Wisconsin Madison





研究方向:

1.) Writing, reading and editing a molecular language/code. Currently, they are addressing the fundamental hypothesis that the combinatorial nature of nucleosomal PTM (post-translational modification) states are specifically recognized and acted upon by enzyme complexes containing multivalent readers. They and others have proposed that combinatorial posttranslational modifications (PTMs) give rise to a histone „code‟ or „language‟, which is interpreted by enzyme complexes to mediate transcriptional responses (e.g., activation or repression). They employ numerous biochemical approaches to investigate the existence of a functional histone code involving enzyme-catalyzed PTMs. 2.) Linking metabolism with the epigenome. They
are testing the hypothesis that certain chromatin modifying complexes have evolved to exquisitely „sense‟ metabolite levels and respond accordingly, modifying specific chromatin loci for altered gene expression. 3.) Sirtuins and reversible protein acetylation. They are examining the central hypothesis that reversible protein acetylation is a major regulatory mechanism for controlling diverse metabolic processes, and that at the molecular level, site-specific acetylation alters the intrinsic activity of targeted proteins.


近期发表论文:

1.Krautkramer KA, Kreznar JH, Romano KA, Vivas EI, Barrett-Wilt GA, Rabaglia ME, Keller MP, Attie AD, Rey FE, Denu JM*. Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues. Mol Cell. 2016 Dec 1;64(5):982-992
2.Su Z, Wang F, Lee JH, Stephens KE, Papazyan R, Voronina E, Krautkramer KA, Raman A, Thorpe JJ, Boersma MD, Kuznetsov VI, Miller MD, Taverna SD, Phillips GN Jr, Denu JM*. Reader domain specificity and lysine demethylase-4 family function. Nat Commun. 2016 Nov 14;7:13387.
3.Yu W, Denu RA, Krautkramer KA, Grindle KM, Yang DT, Asimakopoulos F, Hematti P, Denu JM*. Loss of SIRT3 Provides Growth Advantage for B Cell Malignancies. J Biol Chem. 2016 Feb 12;291(7):3268- 79.
4.Kugel S, Feldman JL, Klein MA, Silberman DM, Sebastián C, Mermel C, Dobersch S, Clark AR, Getz G, Denu JM*, Mostoslavsky R*. Identification of and Molecular Basis for SIRT6 Loss-of-Function Point Mutations in Cancer. Cell Rep. 2015 Oct 20;13(3):479-88
5.Dittenhafer-Reed KE, Richards AL, Fan J, Smallegan MJ, Fotuhi Siahpirani A, Kemmerer ZA, Prolla TA, Roy S, Coon JJ, Denu JM*. SIRT3 mediates multi-tissue coupling for metabolic fuel switching. Cell Metab. 2015 Apr 7;21(4):637-46