Cedric R. Clapier

Cedric R. Clapier, PhD, MSc, BSc

Languages spoken: English, French

Academic Information

Departments Primary - Oncological Sciences

Academic Office Information

cedric.clapier@hci.utah.edu

Research Interests

  • Chromatin
  • Gene Expression Regulation
  • Epigenetics in Cancer
  • Biochemistry

Dr. Clapier received his B.Sc. in Biochemistry and his M.Sc. (high honors) in Cellular and Molecular Biology from the Joseph Fourier University in Grenoble, France. In 1997, he was selected by the international PhD programme of the European Molecular Biology Laboratory (EMBL) located in Heidelberg, Germany. During his graduate work conducted with Prof. Peter B. Becker on chromatin remodeling, he pioneered the production and usage of recombinant chromatin in biochemical characterization of remodelers in vitro, and discovered the first direct regulation of a chromatin remodeler (ISWI) by a nucleosome feature (the histone H4 tail basic-patch). He received his PhD (highest honors) in Molecular and Cellular Biology in 2001 as a joint degree from EMBL and the Joseph Fourier University. In 2002, Dr. Clapier investigated aspects of transcription regulation by chromatin with Dr. Jerry L. Workman at Penn State University. He then did a postdoctoral training in structural biology with Dr. Christoph W. Müller at the EMBL Grenoble outstation for which he received an EMBO long-term fellowship. During his postdoctoral work, Dr. Clapier made decisive biochemical contribution leading to the crystallization and structure of the rabies virus nucleoprotein, and solved the crystal structure of Drosophila melanogaster nucleosome. In 2007, he joined the laboratory of Prof. Bradley R. Cairns at the Huntsman Cancer Institute, University of Utah, where he made landmark discoveries in the regulatory architecture and logic of chromatin remodelers. First, Dr. Clapier demonstrated that ISWI remodeler is an intrinsically active DNA translocase held in check by two newly discovered flanking regions acting as intrinsic brakes of ATPase activity and coupling, a measurement of DNA translocation efficiency. Regulated activation of the remodeler is achieved by selective inhibitions of those intrinsic inhibitions by specific nucleosomal epitopes. These discoveries ruled out the power stroke model for the mechanism of chromatin remodeling. In a separate study, Dr. Clapier demonstrated that the capacity of the SWI/SNF-subfamily of remodelers to perform nucleosome ejection, rather than sliding, is potentiated by the regulation of a continuum of DNA translocation efficiency, with the conserved Actin-Related Proteins being required for nucleosome ejection by upregulating coupling.

Dr. Clapier is currently a Research Associate Professor at the Huntsman Cancer Institute and the Department of Oncological Sciences of the University of Utah, School of Medicine. His research continues to focus on the mechanistic characterization of the regulatory architecture and logic of chromatin remodelers, as well as on the misregulations of DNA translocation resulting from mutations observed within chromatin remodelers in cancers.

Dr. Clapier has presented his research work in many international venues as the FASEB, ASBMB, Keystone and EMBO conferences. He also authored a book chapter and reviews internationally recognized as reference publications for the field of chromatin remodeling. Dr. Clapier taught ‘Epigenetics & Chromatin Remodeling’ in the ‘Nucleic Acids’ course and was a jury member for the oral exams during five years at the Graduate School of the Joseph Fourier University. He is currently a case-based learning discussion leader for first year medical students at the University of Utah, School of Medicine.

Research Statement

<p><font color="#000000" face="Calibri" size="3">While all cells in an organism harbor the same genome, different cell types and functions need to be established and maintained. In parallel, to accommodate a broad variety of DNA transactions required during their life, each cell needs a dynamic and responsive access to its genome. The packaging of genomic DNA into chromatin provides an opportunity to encompass all these requirements. Among epigenetic regulators influencing chromatin, chromatin remodelers are molecular machines that dynamically sculpture diverse chromatin landscapes and change DNA accessibility by performing highly regulated ATP-dependent DNA translocation in the context of nucleosomes.</font></p>
<p><font color="#000000" face="Calibri" size="3">My research focuses on understanding at the molecular level the fundamental mechanisms and regulations controlling the activities of chromatin remodelers as well as their alterations in cancers with the perspective of developing new therapeutic approaches.</font></p>

Education History

Doctoral Training European Molecular Biology Laboratory - Peter B. Becker, Ph.D.
 PhD
Joseph Fourier University
 MSc
Undergraduate Joseph Fourier University
 BSc

Selected Publications

Journal Article

  1. Clapier CR (2021). Sophisticated Conversations between Chromatin and Chromatin Remodelers, and Dissonances in Cancer. Int J Mol Sci, 22(11).
  2. Clapier CR, Verma N, Parnell TJ, Cairns BR (2020). Cancer-Associated Gain-of-Function Mutations Activate a SWI/SNF-Family Regulatory Hub. Mol Cell, 80(4), 712-725.e5.
  3. Ye Y, Wu H, Chen K, Clapier CR, Verma N, Zhang W, Deng H, Cairns BR, Gao N, Chen Z (2019). Structure of the RSC complex bound to the nucleosome. Science, 366(6467), 838-843.
  4. Cakiroglu A, Clapier CR, Ehrensberger AH, Darbo E, Cairns BR, Luscombe NM, Svejstrup JQ (2019). Genome-wide reconstitution of chromatin transactions reveals that RSC preferentially disrupts H2AZ-containing nucleosomes. Genome Res, 29(6), 988-998.
  5. Clapier CR, Iwasa J, Cairns BR, Peterson CL (2017). Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nat Rev Mol Cell Biol, 18(7), 407-422.
  6. Clapier CR, Kasten MM, Parnell TJ, Viswanathan R, Szerlong H, Sirinakis G, Zhang Y, Cairns BR (2016). Regulation of DNA Translocation Efficiency within the Chromatin Remodeler RSC/Sth1 Potentiates Nucleosome Sliding and Ejection. Mol Cell, 62(3), 453-461.
  7. Clapier CR, Cairns BR (2012). Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes. Nature, 492(7428), 280-4.
  8. Sirinakis G, Clapier CR, Gao Y, Viswanathan R, Cairns BR, Zhang Y (2011). The RSC chromatin remodelling ATPase translocates DNA with high force and small step size. EMBO J, 30(12), 2364-72.
  9. Clapier CR, Cairns BR (2009). The biology of chromatin remodeling complexes. Annu Rev Biochem, 78, 273-304.
  10. Clapier CR, Chakravarthy S, Petosa C, Fernndez-Tornero C, Luger K, Mller CW (2008). Structure of the Drosophila nucleosome core particle highlights evolutionary constraints on the H2A-H2B histone dimer. Proteins, 71(1), 1-7.
  11. Albertini AA, Clapier CR, Wernimont AK, Schoehn G, Weissenhorn W, Ruigrok RW (2007). Isolation and crystallization of a unique size category of recombinant Rabies virus Nucleoprotein-RNA rings. J Struct Biol, 158(1), 129-33.
  12. Albertini AA, Wernimont AK, Muziol T, Ravelli RB, Clapier CR, Schoehn G, Weissenhorn W, Ruigrok RW (2006). Crystal structure of the rabies virus nucleoprotein-RNA complex. Science, 313(5785), 360-3.
  13. Grne T, Brzeski J, Eberharter A, Clapier CR, Corona DF, Becker PB, Mller CW (2003). Crystal structure and functional analysis of a nucleosome recognition module of the remodeling factor ISWI. Mol Cell, 12(2), 449-60.
  14. Corona DF, Clapier CR, Becker PB, Tamkun JW (2002). Modulation of ISWI function by site-specific histone acetylation. EMBO Rep, 3(3), 242-7.
  15. Clapier CR, Nightingale KP, Becker PB (2002). A critical epitope for substrate recognition by the nucleosome remodeling ATPase ISWI. Nucleic Acids Res, 30(3), 649-55.
  16. Clapier CR, Lngst G, Corona DF, Becker PB, Nightingale KP (2001). Critical role for the histone H4 N terminus in nucleosome remodeling by ISWI. Mol Cell Biol, 21(3), 875-83.
  17. Brehm A, Lngst G, Kehle J, Clapier CR, Imhof A, Eberharter A, Mller J, Becker PB (2000). dMi-2 and ISWI chromatin remodelling factors have distinct nucleosome binding and mobilization properties. EMBO J, 19(16), 4332-41.
  18. Corona DF, Lngst G, Clapier CR, Bonte EJ, Ferrari S, Tamkun JW, Becker PB (1999). ISWI is an ATP-dependent nucleosome remodeling factor. Mol Cell, 3(2), 239-45.

Review

  1. Kasten MM, Clapier CR, Cairns BR (2011). SnapShot: Chromatin remodeling: SWI/SNF. [Review]. Cell, 144(2), 310.e1.

Book Chapter

  1. Clapier CR, Cairns BR (2014). Chromatin Remodeling Complexes. In J. Workman & SM Abmayr (Eds.), Fundamentals of Chromatin (pp. 69-146). Springer.