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Systems Biology and Medicinal Chemistry

Biochemistry of Epigenetic Inheritance

Under the direction of Nicole Francis

Research Unit

The ability of cells to acquire and maintain stable differentiated states is central to development. Nicole J. Francis’s lab is interested in how the gene expression patterns that define cellular states can be inherited across cell generations and how this might involve heritable changes to chromatin. The idea that chromatin structure carries heritable (epigenetic) information is attractive because of its conceptual simplicity—epigenetic and genetic information are inherited together. However, this idea raises questions about how chromatin features can be inherited through cell cycles since both DNA replication and mitosis disrupt chromatin structure. 

The goal of the team’s work is to discover the biochemical mechanisms that enable chromatin states to be propagated through DNA replication and mitosis. They address these questions using the Polycomb Group (PcG) proteins of Drosophila melanogaster.

Nicole Francis

Research Unit Director

Phone:
514 987-5558
  • Director, Systems Biology and Medicinal Chemistry Research Division
  • Director, Biochemistry of Epigenetic Inheritance Research Unit
  • Associate IRCM Research Professor
  • Associate Research Professor, Department of Biochemistry and Molecular Medicine, Université de Montréal
  • Research Scholar from the John-R.-Evans Leaders Fund, Canada Foundation for Innovation

Awards and honours

  • Searle Scholar Award, Kinship Foundation
  • Basil O’Connor Scholar Award, March of Dimes
  • New Scholar Award, The Ellison Medical Foundation

Degrees and relevant experience

  • B.Sc. in Biology, McGill University, Montreal, QC (1989-1993)
  • PhD in Neuroscience, Case Western Reserve University, Cleveland, OH (1993-2000)
  • Postdoctoral fellowship with Dr. Robert Kingston, Department of Molecular Biology, Massachusetts General Hospital (2000-2004), Boston, MA
  • Assistant Professor, Molecular and Cellular Biology, Harvard University, Cambridge, MA (2004-2008)
  • Associate Professor, Molecular and Cellular Biology, Harvard University, Cambridge, MA (2008-2012)

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Nicole Francis
Research Unit Director
Phone:
514 987-5558
Celia Alecki
PhD student
Aurélie Huang-Sung
M.Sc. student
Alexander Kaltashov
Undergraduate Student
Jin Joo Kang
Postdoctoral Fellow
Yoon Soon Kang
Postdoctoral Fellow
Julien Malette
Research Assistant
Pandimadevi Djamouna Sihou
PhD Student
Mélanie Candido
Administrative Assistant
Phone:
514 987-5639

Projects and major discoveries

  • How are chromatin states propagated though DNA replication

    Current projects involve analyzing the behaviour of both PcG proteins and histones during DNA replication, and how chromatin structure is restored after DNA replication.

  • How are chromatin states propagated though mitosis

    Current work aims to determine how and why PcG proteins are lost from some sites in mitosis but not others. Specifically the lab is interested in the chromatin structure of both types of sites in interphase and mitosis, and how PcG proteins are recruited to them. 

Publications

Madamba, E.V., Berthet, E.B., and Francis, N.J. (2017) Inheritance of histones H3 and H4 during DNA replication in vitro. Cell Reports 5: 1361-1374 PMID 29091772.

Wani, A.H.*, Boettiger, A.N.*, Schorderet, P., Ergun, A., Munger, C., Sadreyev, R.I., Zhuang, X., Kingston, R.E., and Francis, N.J. (2016) Chromatin topology is coupled to Polycomb group protein subnuclear organization. Nat. Commun. 13:10291 PMID 26759081. 

Follmer, N.E., Wani, A.H. and Francis, N.J. (2012) Polycomb Group proteins are retained at specific sites on chromatin in mitosis. PLoS Genet 8(12): e1003135. doi:10.1371/journal.pgen.1003135. 

Lo, S.M., McElroy, K.A. and Francis, N.J. (2012) Chromatin modification by PSC occurs at one PSC per nucleosome and does not require the acidic patch of histone H2A. PLoS ONE 7(10): e47162. doi:10.1371/journal.pone.0047162. PMID: 23071745

Lengsfeld, B.M., Berry, K.N., Ghosh, S., Takahashi, M., and Francis, N.J. (2012) A Polycomb complex remains bound through DNA replication in the absence of other eukaryotic proteins. Sci. Rep. 2: 661. PMID:22993687.

Lo, S.M.*, Follmer, N.E.*, Lengsfeld, B.M., Madamba, E.V., Seong, S., Grau, D.J., and Francis, N.J. (2012) A Bridging model for persistence of a Polycomb Group protein complex through DNA replication. Mol. Cell 46: 784-796. PMID: 22749399.

Beh, L.Y., Colwell, L.J., and Francis, N.J. (2012) A core subunit of Polycomb repressive complex 1 is broadly conserved in function but not primary sequence. PNAS, 109(18):E1063-71. PMID:22517748

Lo, S.M. and Francis, N.J. (2010) Inhibition of Chromatin Remodeling by Polycomb Group Protein Posterior Sex Combs Is Mechanistically Distinct from Nucleosome Binding.  Biochemistry 49:9438-9448.  PMID:  20873869.

Grau, D.J., Chapman, B.A., Garlick, J.D., Borowsky, M., Francis, N.J., Kingston, R.E. (2011) Compaction of chromatin by diverse Polycomb group proteins requires localized regions of high charge. Genes Dev., 25:2210-21. PMID: 22012622

Francis, N.J., Follmer, N.E., Simon, M.D., Aghia, G., and Butler, J.D. (2009) Polycomb proteins remain bound to chromatin and DNA during replication in vitro. Cell, 137: 110-122.  PMID: 19303136.
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Systems Biology and Medicinal Chemistry