ZFIN ID: ZDB-PERS-960805-356
Martin, C. Cristofre
Email: crmartin@science.uottawa.ca
URL: http://www.science.uottawa.ca/bio/prof/Martin/default.htm
Affiliation: Cristofre Martin Lab
Address: Department of Biology University of Ottawa 30 Marie Curie Street Box 450, Station A Ottawa, K1N 6N5 Canada
Country: Canada
Phone: (613) 562-5800 ext6328
Fax: (613) 562-5486

B.Sc., Dept of Zoology, Univerisity of Manitoba, Winnipeg, Manitoba. 1992
M.Sc., Dept of Zoology, University of Manitoba, Winnipeg, Manitoba. 1994
Ph.D., Dept. of Anatomy and Neuro., Loeb Institute, University of Ottawa, Ottawa, Ontario. 1997

Epigenetic Control of Gene Regulation:

The generation of a multicellular organism from a fertilized egg requires the establishment of multiple cell lineages with distinct properties. In vertebrates, the establishment of diverse cell lineages, each committed to a defined differentiation pathway, is believed in part to be dependent upon epigenetic processes that limit the array of genes that are expressed, and thus define the cellular phenotype.
DNA methylation occurs by the addition of a methyl-group to position 5 of cytosine by the enzyme DNA methyltransferase (MTase). This modification has several characteristics that make it an attractive mechanism that may account for much of the epigenetic control of gene regulation that occurs during normal embryonic development. DNA methylation affects the ability of transcriptional regulatory proteins to bind DNA, including repressor proteins like MeCP1 and MeCP2 (methyl-cytosine binding proteins), as well as affecting nucleosome positioning. Increases in DNA methylation are associated with gene silencing, and reductions in DNA methylation are often associated with gene activation. Furthermore, DNA methylation patterns can be preserved through the replication process by the action of maintenance methylases which use the replicated hemimethylated DNA as a template. DNA methylation can be removed by passive demethylation if methylation after replication is suppressed and possibly by active demethylation. As a result, DNA methylation is clonally heritable, stable, and reversible and, thus, satisfies the major requirements for an epigenetic mechanism that can control gene expression.
DNA methylation has been shown to be involved in a number of different biological processes (primarily in mammals) including genomic imprinting, X-chromosome inactivation, and gene silencing. Abnormal DNA methylation has been implicated in a wide range of human diseases including cancer.

We use molecular biology techniques such as PCR, mRNA differential display, in situ hybridization, and DNA chip microarrays to identify, clone and characterize genes that are expressed during zebrafish development and whose transcription is regulated by DNA methylation.

Epigenetic Toxins:

A number of compounds and heavy metals have been identified that can affect normal DNA chromatin structure by altering DNA methylation or histone acetylation. Many of these elements and compounds are found and used in our environment. Perterbations in these epigenetic processes such as DNA methylation and histone acetylation can lead to abnormal gene expression. We are using the zebrafish model system to evaluate the potential of these elements and compounds to affect gene expression in vivo and normal vertebrate development.


Transcription of the zebrafish hsp10 and hsp60 (heat shock proteins) genes are driven by a single bi-directional promoter that is heat inducible. We are developing a transgene construct containing these promoter sequences. This construct will allow expression, in the zebrafish embryo, two genes simultaneous from a single transgene construct. Ectopic expression of the transgene can be achieved by heat shocking the zebrafish embryo, and expression of the transgene in a single cells or tissues can be achieved using lasers. We will use this transgene construct to address questions of gene function in the zebrafish embryo.
Related projects include promoter analysis, and investigating transgene applications for gene therapy.

Coverdale, L.E., Burton, L.E., and Martin, C.C. (2008) High-throughput whole mount in situ hybridization of zebrafish embryos for analysis of tissue-specific gene expression changes after environmental perturbation. Methods in molecular biology (Clifton, N.J.). 410:3-14
Coverdale, L.E., Martyniuk, C.J., Trudeau, V.L., and Martin, C.C. (2004) Differential expression of the methyl-cytosine binding protein 2 gene in embryonic and adult brain of zebrafish. Brain research. Developmental brain research. 153(2):281-287
Pillai, R., Coverdale, L.E., Dubey, G., and Martin, C.C. (2004) Histone deacetylase 1 (HDAC-1) required for the normal formation of craniofacial cartilage and pectoral fins of the zebrafish. Developmental Dynamics : an official publication of the American Association of Anatomists. 231(3):647-654
Martin, C.C., Tsang, C.H., Beiko, R.G., and Krone, P.H. (2002) Expression and genomic organization of the zebrafish chaperonin gene complex. Genome. 45(5):804-811
Martin, C.C., Tang, P., Barnardo, G., and Krone, P.H. (2001) Expression of the chaperonin 10 gene during zebrafish development. Cell stress & chaperones. 6(1):38
Sass, J.B., Martin, C.C., and Krone, P.H. (1999) Restricted expression of the zebrafish hsp90alpha gene in slow and fast muscle fiber lineages. The International journal of developmental biology. 43(8):835-838
Lele, Z., Hartson, S.D., Martin, C.C., Whitesell, L., Matts, R.L., and Krone, P.H. (1999) Disruption of zebrafish somite development by pharmacologic inhibition of hsp90. Developmental Biology. 210(1):56-70
Martin, C.C., Laforest, L., Akimenko, M.-A., and Ekker, M. (1999) A role for DNA methylation in gastrulation and somite patterning. Developmental Biology. 206:189-205
McGowan, R.A. and Martin, C.C. (1997) DNA methylation and genome imprinting in the zebrafish, Danio rerio: some evolutionary ramifications. Biochemistry and cell biology = Biochimie et biologie cellulaire. 75:499-506
Martin, C.C. (1997) DNA methyltransferase in the zebrafish Danio rerio: 5-aza-cytidine treatment of embryos in vivo causes disruption in the development of the axial mesoderm. Ph.D. Thesis.
Ellies, D.L., Langille, R.M., Martin, C.C., Akimenko, M.A., and Ekker, M. (1997) Specific craniofacial cartilage dysmorphogenesis coincides with a loss of dlx gene expression in retinoic acid-treated zebrafish embryos. Mechanisms of Development. 61(1-2):23-36
Ekker, M., Speevak, M.D., Martin, C.C., Joly, L., Giroux, G., and Chevrette, M. (1996) Stable transfer of zebrafish chromosome segments into mouse cells. Genomics. 33:57-64
Martin, C.C. and McGowan, R. (1995) Genotype-specific modifiers of transgene methylation and expression in the zebrafish, Danio rerio. Gen. Res.. 65:21-28
Martin, C.C. and McGowan, R. (1995) Parent-of-origin specific effects on the methylation of a transgene in the zebrafish, Danio rerio. Developmental genetics. 17:233-239
Martin, C.C. (1994) Modifiers of transgene methylation and expression, and genomic imprinting in the zebrafish, Danio rerio. Master's Thesis.

R.W. Flint, R. Gordon, C.C. Martin & G.W. Brodland (1989). Simulation of inversion of amphibian eggs in a gravitational field using hollow glass spheres. (Invited) European Space Agency Bulletin, Noordwijk, The Netherlands. Selected Proceedings of the Workshop on Microgravity as a Tool in Developmental Biology, 11th International Congress of The International Society of Developmental Biologists, Aug 20-25, 1989. Utrecht.

G.W. Brodland, R. Gordon, M.J. Scott, N.K. Bjorklund, K.B. Luchka, C.C. Martin, C. Matuga, M. Globus, S. Vethamany-Globus & D. Shu (1994). Furrowing surface contraction wave coincident with primary neural induction in amphibian embryos. Journal of Morphology 219: 131-142.

C.C. Martin & R. Gordon (1995). Differentiation trees, a junk DNA molecular clock, and the evolution of neoteny in salamanders. Journal of Evolutionary Biology 8: 339-354.

C. C. Martin & C. Sapienza (1999). A role for modifier genes in genome imprinting. In Results and Problems in Cell Differentiation. R. Ohlsson (Ed.). Springer Verlag 25:251-70.