IDENTIFICATION

Name : Jacques
Surname : Côté
University Title : Full Professor
Affiliation to Université Laval : Medical Biology, Medicine
Diploma : Ph.D.
Telephone (office) : (418) 525-4444 ext.: 15545
Telephone (laboratory) : (418) 525-4444 ext.: 15535
Fax : (418) 691-5439
Email : jacques.cote@crhdq.ulaval.ca

RESEARCH INTERESTS

It is now clear that the reconfiguration of the chromosome structure is a crucial step in the processes that control the expression and stability of the human genome, and consequently differentiation/cell proliferation and their deregulation leading to diseases like cancer. The activities involved in this reconfiguration include multiprotein complexes that alter the basic unit of chromosomes, i.e. the nucleosome, where DNA is wrapped around a protein core. These complexes are closely linked to the control of gene transcription, DNA replication and repair. These activities interact as well with oncogenes and tumor suppressors and are the basis of the epigenetic phenomena. Our work aims to characterize these multiprotein complexes and understand their mechanisms of action. This will provide very important information on the basic events controlling the expression and maintenance of the eukaryotic genome and cell proliferation.

The transcriptional regulation of genes is a fundamental process of cellular life. Indeed, it is the expression of proteins at key moments during the cell cycle and tissue differentiation that allows a cell to live, grow, divide and perform its specific task in response to various signals. Where there is deregulation of this process, it leads to malfunctioning cells, which may lead to uncontrolled proliferation (cancer) or death. Much of this control is linked to the dynamic configuration of the packaging of the genetic material in the cell: a structure called chromatin. Our research is focused on the role and mechanisms of action of protein complexes modifying the structure of chromatin in transcriptional regulation.

Another event that could lead to disruption of cellular function is the instability of its genome. Indeed, the accumulation of damage occurring at critical locations in the DNA can have dire consequences as the formation of cancerous cells. To counter this phenomenon, the cell has several repair mechanisms, all requiring access to the DNA damage. For this reason the study of the role of chromatin remodeling complexes in DNA repair and DNA damage signaling is essential.

Using techniques of molecular biology, biochemistry and genetics, as well as proteomics and functional genomics, our research aims to elucidate the precise function of these complexes in the expression and preservation of the integrity of genetic material. The information we acquire can be used in the development of drugs / diagnostic tools targeting these molecular events in the fight against cancer, in terms of prevention as well as treatment of the disease itself.

RESEARCH PROJECTS

Chromatin modifications during transcription, replication and DNA repair; the role of tumor suppressor acetyltransferase complexes and their functional partners


The ING family of tumor suppressors is highly conserved among eukaryotes and every members of this family are part of specific protein complexes that modulate acetylation of chromatin. Some are recruited to regulate gene expression, others appear to sites of DNA damage to facilitate repair or follow the polymerase to allow duplication of the genetic material.
The laboratory's research projects use the powerful yeast model system and human cells in culture to characterize the roles and mechanisms of action of these protein complexes in nuclear functions in eukaryotic cells.

1) Regulation and impact of the NuA4/Tip60 histone acetyltransferase complex in transcriptional regulation and the repair of DNA double-strand breaks.
a- Structural and functional characterization of the complex and its various subunits.
b-Mechanisms of recruitment to promoters and sites of DNA damage.
c-functional relationship with the incorporation of histone variants in chromatin.

2) Structural and functional characterization of other acetyltransferase/deacetylase complexes containing an ING tumor suppressor.

3) Role of histone modifications in the establishment of euchromatin-heterochromatin boundaries.

4) Role and functional intreractions of ING acetyltransferases complexes necessary for replication of the genome.













Figure 1: Electron microscopy imaging of the SWI/SNF ATP-dependent chromatin remodeling complex interacting with a nucleosomal array (a,b: nucleosome array alone; c: array plus SWI/SNF).



Figure 2: The NuA4 Histone Acetyltransferase complex

Figure 3: Immunofluorescence imaging of the Esa1 HAT protein in diploid yeast cells (DNA in blue, Esa1 in green).

Figure 4: Immunofluorescence imaging of the Esa1 HAT protein during yeast cell division (DNA in red, Esa1 in green).

Figure 5: Diverse functions of multi-subunit HAT complexes.

FUNDING

Funding agency

Type of funding

Project title

Canadian Institutes of Health Research

Operating grant

"Dissection of the NuA4 acetyltransferase complex in nuclear functions"

Canadian Institutes of Health Research

Operating grant

"Regulation of nuclear processes and cell fate by MYST-ING tumor suppressor complexes"

Canada Research Chairs

Research Chair, Tier I

"Canada Research Chair in Chromatin Biology and Molecular Epigenetics"

Canadian Institutes of Health Research-CEEHRC

Catalyst grant

“Functional analysis of non-coding RNA/chromatin interactions at imprinted Prader-Willi Syndrome locus”

PUBLICATIONS

(partial, for complete list on PubMed, Click on this link)

Since 2011

M.-E. Lalonde, N. Avvakumov, K. C. Glass, F.-H. Joncas, N. Saksouk, E. Paquet, K. Yan, M. Holliday, S. Tan, X.-J. Yang, T, G. Kutateladze and J. Côté (2013) “Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity”. Genes Dev., in press.

A.-L Steunou, D. Rossetto and J. Côté (2013) “Regulating chromatin by histone acetylation”. Fundamentals of Chromatin, edited by J.L. Workman for Springer. In press.

Bilodeau S, Côté J. (2012) "A chromatin switch for chromosome condensation". Dev Cell, 23:1127-8.

C.A. Musselman, M.-E. Lalonde, J. Côté and T. G. Kutateladze (2012) “Perceiving the epigenetic landscape through histone readers”. Nature Struct Mol Biol., 19: 1218-1227.

C. Musselman, N. Avvakumov, R. Watanabe, C. G. Abraham, M.-E. Lalonde, Z. Hong, C. Allen, S. Roy, J. Nunez, J. Nickoloff, C. A. Kulesza, A. Yasui, J. Côté, and T. G. Kutateladze (2012) “Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1”. Nature Struct Mol Biol., 19: 1266-1272.

Rossetto D, Avvakumov N, Côté J. (2012) "Histone phosphorylation: A chromatin modification involved in diverse nuclear events". Epigenetics. 7:1098-108.

N. Avvakumov*, M.-E. Lalonde*, N. Saksouk, E. Paquet, K. C. Glass, A.-J. Landry, Y. Doyon, C. Cayrou, G. Robitaille, D. Richard, X.-J. Yang, T. G. Kutateladze and J. Côté (2012) “Conserved molecular interactions within HBO1 acetyltransferase complexes regulate cell proliferation”. Mol Cell Biol, 32:689-703.

P. Billon and J. Côté (2012) “Precise deposition of histone H2A.Z in chromatin for genome expression and maintenance”. Biochem Biophys Acta, 1819:290-302.

H. Yuan , D. Rossetto , H. Mellet , W. Dang , M. Srinivasan , J. Johnson , S. Hodawadekar , E. Ding , K. Speicher , N. Abshiru , R. Perry , D. Speicher , P. Thibault , A. Verreault , F. Johnson , S. Berger , R. Sternglanz , S. McMahon , J. Côté and R. Marmorstein (2011) “MYST Protein Acetyltransferase Activity Requires Active Site Lysine Autoacetylation”. EMBO J., 31:58-70.

J.R. Chittuluru, Y. Chaban, , J. Monnet-Saksouk M.J. Carrozza, V. Sapountzi, W. Selleck, J. Huang, R.T. Utley, M. Cramet, S. Allard, G.Cai, J.L. Workman, M. Fried, S. Tan, J. Côté* and F.J. Asturias* (2011) “Structure and nucleosome interaction of the NuA4 and Piccolo-NuA4 histone acetyltransferase complexes”. Nature Struct. Mol. Biol., 18:1196-203.

N. Avvakumov, A. Nourani and J. Côté (2011) “Histone Chaperones: Modulators of Chromatin Marks”. Mol. Cell, 41: 502-14.

V. Sapountzi and J. Côté (2011) “MYST-family histone acetyltransferases: beyond chromatin”. Cell. Mol. Life Sci., 68: 1147-56.


2006 - 2010

D. Rossetto, A.W. Truman, S.J. Kron and J. Côté (2010) “Epigenetic modifications in double strand break DNA damage signaling and repair”. Clin. Cancer Res., 16:4543-4552.

G.G. Sharma, S. So, A. Gupta, R. Kumar, C. Cayrou, N. Avvakumov, U. Bhadra, R.K. Pandita, M.H. Porteus, D.J. Chen, J. Côté and T.K. Pandita (2010) “MOF and histone H4 acetylation at lysine 16 are critical for DNA Damage Response”. Mol. Cell. Biol., 30:3582-3595.

M. Altaf, A. Auger, J. Monnet-Saksouk, J. Brodeur, S. Piquet, M. Cramet, N. Bouchard, N. Lacoste, R.T. Utley, L. Gaudreau and J. Côté (2010) “NuA4-dependent acetylation of nucleosomal histone H4 and H2A directly stimulates incorporation of H2A.Z by the SWR1 complex”. J. Biol. Chem., 285:15966-15977.

C.C. Nnakwe, M. Altaf, J. Côté and S. J. Kron (2009) “Dissection of Rad9 BRCT Domain Function In The Mitotic Checkpoint Response To Telomere Uncapping”. DNA Repair, 8:1452-61.

N. Saksouk, N. Avvakumov, K.S. Champagne, T. Hung, Y. Doyon, C. Cayrou, E. Paquet, M. Ullah, A.-J. Landry, V. Côté, X.-J. Yang, O. Gozani, T. G. Kutateladze and J. Côté (2009) "HBO1 HAT Complexes Target Chromatin throughout Gene Coding Regions via Multiple PHD Finger Interactions with Histone H3 Tail". Mol. Cell, 33: 257-265.

M. Altaf, A. Auger, M. Covic and J. Côté (2009) “Connection between histone H2A variants and chromatin remodeling complexes”. Bioch. Cell. Biol., 87: 35-50.

Santos-Rosa H, Kirmizis A, Nelson C, Bartke T, Saksouk N, Cote J, Kouzarides T. (2009) "Histone H3 tail clipping regulates gene expression". Nat Struct Mol Biol, 16:17-22.

M. Ullah, N. Pelletier, L. Xiao, S. P. Zhao, K. Wang, C. Degerny, S. Tahmasebi, C. Cayrou, Y. Doyon, S. L. Goh, N. Champagne, J. Côté and X.-J. Yang (2008) “Molecular Architecture of Quartet MOZ/MORF Histone Acetyltransferase Complexes”. Mol. Cell. Biol., 28:6828-43.

K. S. Champagne, N. Saksouk, P. V. Peña, K. Johnson, M. Ullah, X.-J. Yang, J. Côté and T. G. Kutateladze (2008) “The crystal structure of the ING5 PHD finger in complex with an H3K4me3 histone peptide”. Proteins, 72: 1371-1376.

N. Saksouk, N. Avvakumov and J. Côté (2008) "(de)MYSTification and INGenuity of tumor suppressors". Cell Mol Life Sci, 65: 1013-8.

A. Auger, L. Galarneau, M. Altaf, A. Nourani, Y. Doyon, R.T. Utley, D. Cronier, S. Allard and J. Côté (2008) “Eaf1 is the platform for NuA4 molecular assembly that evolutionarily links chromatin acetylation to ATP-dependent exchange of histone H2A variants”. Mol. Cell. Biol., 28: 2257-70.

M. Altaf, R.T. Utley, N. Lacoste, S. Tan, S. Briggs and J. Côté (2007) “Interplay of chromatin modifiers on histone H4 tail defines the boundary of telomeric heterochromatin”. Mol. Cell, 28: 1002-1014.

C.D. Allis, S.L. Berger, J. Côté, S. Dent, T. Jenuwien,, T. Kouzarides, L. Pillus, D. Reinberg, Y. Shi, R. Shiekhattar, A. Shilatifard, J. Workman and Y. Zhang (2007) “New Nomenclature for Chromatin-Modifying Enzymes”. Cell, 131: 633-636.

N. Avvakumov and J. Côté (2007) “The MYST family of histone acetyltransferases and their intimate links to cancer”. Oncogene, 26: 5395-407.

M. Altaf, N. Saksouk and J. Côté (2007) "Histone modifications in response to DNA damage". Mutation Res., 618: 81-90.

N. Avvakumov and J. Côté (2007) "Functions of MYST family histone acetyltransferases and their link to disease". Subcellular Biochemistry, “Chromatin and Disease”, 41: 295-318.

A. Javaheri, R. Wysocki, O. Jobin-Robitaille, M. Altaf, J. Côté and S.J. Kron (2006) “Yeast G1 DNA damage checkpoint regulation by H2A phosphorylation is independent of chromatin remodeling“. Proc. Natl. Acad. Sci. U.S.A., 103: 13771-13776.

X. Shi, T. Hong, K. Walter, M. Ewalt, E. Michishita, T. Hung, D. Carney, F. Lan, M. R. Kaadige, N. Lacoste, C. Cayrou, P. Pena, F. Davrazou, D. E. Ayer, Y. Shi, T. G. Kutateladze, J. Côté, K. F. Chua and O. Gozani (2006) “ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression“. Nature, 442: 96-99.

Y. Doyon, C. Cayrou, M. Ullah, A.-J. Landry, V. Côté, W. Selleck, W.S. Lane, S. Tan, X.-J. Yang and J. Côté (2006) “ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation”. Mol. Cell, 21: 51-64.


Before 2006

Click on this link

TEAM MEMBERS


Name: Valérie Côté, B.Sc.                        
Position: Research assistant
Email: valerie.cote@crhdq.ulaval.ca

The Lab Manager



Name: Rhea T. Utley, Ph.D.                               
Position: Research associate
Email: rhea.utley@crhdq.ulaval.ca



Name: Nikita Avvakumov, Ph.D.                              
Position: Research associate
Email : nikita.avvakoumov.1@ulaval.ca



Name: Dorine Rossetto, M.Sc.                              
Position: Ph.D. student
Email : rossettodorine@yahoo.fr



Name : Marie-Eve Lalonde, M.Sc.                    
Position : Ph.D. student
Email : marie-eve.lalonde.3@ulaval.ca



Name: Céline Roques, Ph.D.                               
Position: Research assistant
Email : roquesceline@yahoo.fr



Name : Pierre Billon, M.Sc.                        
Position : Ph.D. student
Email : billon.pierre@yahoo.fr



Name : Karine Jacquet, M.Sc.                        
Position : Ph.D. student
Email : karine.jacquet.1@ulaval.ca



Name: Anne-Lise Steunou, Ph.D.                              
Position: Post-doctoral fellow
Email : annelise.steunou@yahoo.com



Lab at the PennState Chromatin meeting, June 2011
(Pierre, Karine, Marie-Eve and Anne-Lise)


Lab's 4th Ph.D. defense!
Dr. Mohd Altaf Bhat, June 11th 2009

(front: Joannie, Marie-Ève, Vasso, Altaf, Dorine, Valérie, Sandra; back: Chloé, Romain, Olivier, Nehmé, Nikita, Myriam, Jacques)


JSE 08/08
(1st row: ; Julie, Joannie, Patricia, Dorine; 2nd row: Olivier, Nehme+Medhi, Jacques, Nikita, Altaf, Myriam)


Lab Retreat at Tadoussac 05/08
(1st row: Vasso, Rhea+Lucas, Valérie+Jacob; 2nd row: Nehme+Medhi, Julie, Olivier, Joannie, Patricia, Dorine, Myriam, Altaf; 3rd row: Nikita, Jacques+Alexis)


Lab 2/08
(1st row: Dorine, Olivier, Altaf, Myriam, Julie; 2nd row: Jacques, Nik, Nehmé, Patricia, Vasso)


Lab at the PSU Chromatin meeting 7/07
(Front: Nehme, Julie, Myriam; Back: Altaf, Olivier, Dorine, Nikita)


Lab's 3rd Ph.D. defense!
Dr. Yannick Doyon, April 20th 2007

(front: Anne-Julie, Jacques+Lucas, Rhea+Alexis, Valérie, Olivier; back: Altaf, Nehmé, Myriam, Yannick, Nik, Amine)

Lab's 2nd Ph.D. defense!
Dr. Andréanne Auger, December 16th 2005

(front: Jacques, Valérie, Anne-Julie; back: Christelle, Rhea, Andrew, Altaf, Yannick, Marcela; +Daniel Malenfant)

Lab's first Ph.D. defense!
Dr. Nicolas Lacoste, Feb. 7th 2005

(Front: Stéphane, Israël, Andréanne, Valérie, Rhea; Back: Anne-Julie, Olivier, Jacques, Nicolas, Yannick)

LAB at the PSU Chromatin meeting 8/03
(Front: Rhea, Jacques, Amine, Andréanne, Olivier; Back: Yannick, Nicolas, Dominique, Anne-Julie)

OTHER INFORMATION

Ex-members of the lab


Name: Vasileia Sapountzi, Ph.D.
Position: Post-doctoral fellow (07-11)
Email : vasileia.sapountzi.1@ulaval.ca



Name: Nehmé Saksouk, Ph.D.
POsition: Post-doctoral fellow (06-10)
Courriel : nehme.saksouk.1@ulaval.ca



Name: Julie Monnet-Saksouk, M.Sc.
position: Master student/research assistant (07-10)
Courriel : julie-saksouk.monnet.1@ulaval.ca



Name : Myriam Cramet, M.Sc.                                           
Position : Master student/Research assistant (07-09, 10-11)
Email : myriam.cramet@free.fr



Name : Mohd Altaf Bhat, Ph.D                    
Position : Ph.D. student (05-09)
Email : altafabd@yahoo.co.in



Name: Patricia Savard, M.Sc.                              
Position: Research assistant (08)
Email: patricia.savard@crhdq.ulaval.ca



Name : Yannick Doyon, Ph.D.                              
Position : Graduate student (01-06)
Email : aporie@hotmail.com



Name: Christelle Cayrou, Ph.D.                              
Position: Post-doctoral fellow (02-06)
Email : christelle.cayrou@gmail.com



Name : Andréanne "Andrew" Auger, Ph.D.
Position : Ph.D. student (01-05)
Email : drewauger@yahoo.ca



Name: Stéphane Allard, M.Sc.                              
Position: Research assistant (97-05)
Email : stephane.allard@gmail.com



Name: Marcela Covic, Ph.D.                             
Position: Post-doctoral fellow (05)
Email : covicmarcela@yahoo.ca



Name : Anne-Julie Landry, M.Sc.                                         
Position : Master student (03-05)/Research assistant (06)
Email : ajulandry@hotmail.com



Name : Israël Fortin, M.Sc.                              
Position : Master student (03-05)
Email : israelf@hotmail.com



Name: Nicolas Lacoste, Ph.D.                              
Position: Ph.D. student (00-04)
Email: nicooch@hotmail.com



Name: Amine Nourani, Ph.D.                              
Position: Post-Doctoral fellow (99-03)
Email: anourani@hotmail.com



Name: Dominique "Doum" Cronier, M.Sc.
Position: Master student, (00-03)
Email: dudu121@hotmail.com



Name: Nathalie "Nat" Bouchard, M.Sc.                      
Position: Master student, (00-02)
Email: bouchard_nat@hotmail.com



Name: Alexandre A. "Alex" Boudreault, M.Sc.
Position: Master student, (99-01)
Email: alexboudreault@hotmail.com



Name: Luc Galarneau, Ph.D.                     
Position: Post-Doctoral fellow (99-01)
Email: lgalarno@mediom.qc.ca



Name: Julie "Ju" Savard, M.Sc.                      
Position: Master student (98-00)
Email: jusavard@videotron.ca



Name: Marie Martineau                              
Position: Undergraduate student (01-04)
Email: pakita_cocoa@hotmail.com



Name : Eijaz Ul- Noor, M.Sc.
Position : Graduate student (10)
Courriel : eijazul@gmail.com



Name : Joannie Roberge                         
Position : Undergraduate student (08-09)
Email : joannie.roberge.1@ulaval.ca



Lab at Sugar Shack 4/06
(1st row: Nehme, Altaf; 2nd row: Valérie, Olivier; 3rd row: Lisa+Nikita, Anne-Julie, Christelle)

Lab at Valcartier 3/06
(Olivier, Lisa+Nikita, Altaf, Nehme, Anne-Julie)

Lab BBQ 7/02
(1st row: Rhea, Jacques, Andréanne, Antoine Allard, Louis Allard, Linda+Anissa+Amine; 2nd row: Dominique, Marie, Stéphane+Marie-France, Nicolas+Cécile; 3rd row: Alexandre, Olivier, Israël; 4th row: Nathalie, Antoine Côté, Yannick)

Lab 10/01
(Back: Jacques, Nathalie, Dominique, Yannick, Stéphane, Amine; Front: Nicolas, Rhea)

LAB 8/99
(Back: Luc, Stéphane, Marie-Eve, Jacques; Front: Amine, Alexandre, Julie)


LAB BBQ 10/01

Interesting links:
-Yeast Proteome Database,
https://www.incyte.com/proteome/YPDsearch-quick.html
-Yeast Genome Database,
http://genome-www.stanford.edu/cgi-bin/SGD/search
-Yeast Protein complex Database,
http://yeast.cellzome.com/index.php
-MDS Proteomics,
http://www.mdsp.com/yeast/
-Yale Genome Analysis Center,
http://ygac.med.yale.edu/
-Nuclear Protein Database,
http://npd.hgu.mrc.ac.uk/index.html
-SMART Protein Domain search
http://smart.embl-heidelberg.de/
-NCBI/PubMed
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed