The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Friday Science Review: May 18, 2012

The development and application of large scale studies of pathways, metabolites and interactions is clearly hugely important for biomedical advances and today’s paper from the University of Toronto and the University of Ottawa is concerned with acetylomics (a relatively recent addition to the rapidly growing omeome).

Lysine acetylation of histones has long been known to be involved in regulation of gene expression. However, acetylation has only recently come to be appreciated as having a wider role outside of histones and may be as extensive a post-translational modification as phosphorylation, with over 2500 mammalian proteins being subject to acetylation. Normal cell proliferation, growth, and differentiation requires the function of lysine acetyltransferases (KATs) and lysine deacetylases (KDACs) to maintain the appropriate levels of histone acetylation and abnormal function of these proteins is found in cancer. Therapeutically, KDACs are the targets of the histone deacetylase inhibitors (e.g. Vorinostat) and also include Sirtuin-1, the proposed target for the much hyped Resveratrol.

In their study, the Andrews lab and collaborators determined a network of 463 synthetic dosage lethal interactions for two classes of KDACs in budding yeast, thereby identifying which cellular pathways were subject to regulation by the different KDACs. The identified genes were enriched for diverse cellular processes, indicating that acetylation has a wide, and currently under-appreciated, role within cells that means we should hope to hear a lot more from acetylomics in the future (whether you be a fan of that particular neologism or not).

Other publications:

  • TLR Tolerance Reduces IFN-Alpha Production Despite Plasmacytoid Dendritic Cell Expansion and Anti-Nuclear Antibodies in NZB Bicongenic Mice. PLoS One. Toronto Western Research Institute
  • Translational Homeostasis via the mRNA Cap-Binding Protein, eIF4E. Molecular Cell. McGill University
  • Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling. PLoS One. University of Western Ontario

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