Charles Brenner Laboratory

  • Metabolic Control of Gene Expression
  • Research Interests

    Cellular function and differentiation depend on an ability to read environmental cues and to execute a gene expression program that is appropriate to time, place and context. Nutrient availability is among the most important signals to which cells respond. Importantly, nutrients are not only transmitted from outside an organism, i.e., by feeding, but are also transmitted from cell to cell and from tissue to tissue. Metabolic control of gene expression is critical to the maintenance of cellular longevity. Dysregulation of the nutritional control of gene expression underlies a series of conditions including nondetection of satiety, which can lead to obesity and diabetes, and diseases such as cancer.

    Our laboratory is engaged in several projects that dissect specific problems in the metabolic control of gene expression. In particular, we are interested in how changing environmental conditions lead to reversible transfer of two carbon, i.e. acetyl, and one carbon, i.e. methyl, groups to proteins and DNA, respectively. These processes are fundamentally important because two carbon transfers link carbohydrate and fat metabolism to nicotinamide adenine dinucleotide (NAD) biosynthesis and because one carbon transfers link the folate cycle and methionine biosynthesis to S-adenosyl methionine metabolism. Trainees in our group are engaged in interdisciplinary projects, performing protein purification, enzymology, structural biology, yeast and somatic cell genetics, genomics, and chemical biology.

    For more information on current projects, see the current research page.

    Recent Publications

    P. Belenky, F.G. Racette, K.L. Bogan, J.M. McClure, J.S. Smith & C. Brenner, "Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD+," Cell, v. 129, pp. 473-484 (2007). Download pdf reprint

    F. Syeda, R.L. Fagan, M. Wean, G.V. Awakumov, J.R. Walker, S. Xue, S. Dhe-Paganon, & C. Brenner, "The RFTS Domain is a DNA-competitive Inhibitor of Dnmt1", JBC, v. 286, pp. 15344-15351 (2011). Dowload pdf reprint

    R.L. Fagan, D.E. Cryderman, L. Kopelovich, L.L. Wallrath & C. Brenner, "Laccaic Acid A is a Direct, DNA-Competitive Inhibitor of DNA Methyltransferase 1," J Biol Chem, v.288, pp. 23858-23867, 2013. DOI: 10.1074/jbc.M113.480517. Download pdf reprint.  

    S. Ghanta, R.E. Grossmann & C. Brenner, "Mitochondrial protein acetylation as a cell-intrinsic, evolutionary driver of fat storage: chemical and metabolic logic of acetyl-lysine modifications" Critical Rev Biochem & Mol Biol, v. 48, pp. 561-574, 2013. Download pdf reprint.  

    Visit Google Scholar for all of Dr. Brenner's publications.

    Secondary Appointment

    Internal Medicine

    Affiliations