Professor and Chair
Room: Roger Guindon Hall, Room 4261 (office), 4257 (lab)
Office: 613-562-5800 ext. 8854 / 8855
Work E-mail: Jean-Francois.Couture@uottawa.ca
The Couture laboratory focuses on using structural biology approaches, such as X-ray crystallography, to understand the molecular underpinnings controlling proteins' functions. While our group focuses predominantly on proteins linked to epigenetic signaling, we have broadened our research interests in developing several fruitful collaborations over the years. Our research group is fortunate enough to be well supported by several funding agencies, including the Canadian Institutes for Health Research, Natural Sciences, and Engineering Research Council, and the Canada Foundation for Innovation to pursue the following projects:
Epigenetics and Leukemia
Epigenetic processes are central to every aspect of cell biology. Our laboratory is interested in fundamental questions of how the interactions between proteins and chromatin shape gene expression, how post-translational modification of chromatin determines the structure of the chromosomes, and how mutations related to cancers such as leukemia sabotage epigenetic processes. We focus on the lysine methyltransferase 2 family (KMT2), a group of enzymes known to be heavily mutated in various forms of aggressive leukemias. The activity of these enzymes is exquisitely dependent on multiple regulatory subunits. Our goals are to understand the mechanisms controlling the association of these proteins with KMT2 enzymes and exploit this information to develop novel therapeutic approaches to treat leukemia.
Lysine methylation and Cancer
Lysine methylation is an essential post-transcriptional modification (PTM) deposited on a large variety of proteins. Recent studies have suggested that many of the enzymes able to deposit this PTM are also linked to various cancers. Yet, the identity of the substrates for each lysine methyltransferase (KMT) remains to be investigated. Our group uses multiple approaches to pair each KMT to their substrates and establish the underlying biological functions.
Structural basis for epigenetic signaling in plants
Like other eukaryotes, plants use epigenetic signaling to control a myriad of biological functions, including, but not limited to, growth, circadian clock, defense against pathogens, and reproduction. Yet, mechanistically, epigenetic signaling in plants has diverged from its mammalian counterparts in various aspects. Our group uses structural biology approaches to decipher these differences with the hope of harnessing the power of epigenetic signaling to improve the plant's biology.
For more information - http://jfclab.ca/
- Yang Y., Joshi M., Takahashi Y.H., Ning Z., Qu Q., Brunzelle J.S., Skiniotis G., Figeys D., Shilatifard A. and Couture J-F. A non-canonical monovalent zinc finger stabilizes the integration of Cfp1 into the H3K4 methyltransferase complex COMPASS. Nucleic Acid Research. (2020), 48, 421-431 (IF = 11.2).
- Qu Q., Takahashi Y., Yang Y., Brunzelle J.S., Couture J-F, Shilatifard A., Skiniotis G. Structure of a histone H3K4 methyltransferase complex. Cell. (2018), 5, 1117-1126 (IF = 30.4).
- Bergamin E., Sarvan S., Malette J., Eram M.S., Yeung S., Mongeon V., Brunzelle J.S., Micheals S.D., Blais A., Vedadi M. and Couture J-F. Molecular Basis for the methylation specificity of ATXR5 for histone H3.1. Nucleic Acid Research, (2017), 45, 6375-6387 (IF = 9.2).
- Zhang P., Tremblay V., Chaturvedi C.P., Skiniotis G., Brand M., Shilatifard A. and Couture J-F. A phosphorylation switch on RbBP5 regulates histone H3 Lys4 methylation. Genes & Development, (2015), 29, 123-8, (IF = 12.6).
- Jacob Y.*, Bergamin E.*, Donoghue M.T.A., Mongeon V., LeBlanc C.A., Voigt P., Underwood C., Brunzelle J.S., Michaels S.D., Reinberg D., Couture J-F# and Martienssen R.#. Selective methylation at lysine 27 on histone H3 variant H3.1 mediates the epigenetic inheritance of heterochromatin during DNA replication. Science, (2014), 343, 1249-1253 (IF = 31.0) # Co-Corresponding author.
- Sarvan S., Avdic V., Tremblay V., Chaturvedi C.P., Zhang P., Lanouette S., Blais A., Brunzelle J.S., Brand M., Couture J-F. Crystal structure of the trithorax group protein Ash2L reveals a Forkhead-like DNA binding domain. Nature Structural and Molecular Biology. (2011) 18, 857-859. (IF = 12.3).