The focus of our laboratory is the function and regulation of eukaryotic DNA methylation. We are taking a genetic approach to the problem to avoid some of the common pitfalls presented by correlative studies and methylation inhibitor experiments. We are using the flowering plant, Arabidopsis thaliana, as an experimental organism, because this plant is one of the few good eukaryotic genetic model systems that methylate their genome. To date, we have isolated seven independent A. thaliana mutants with reduced 5-methylcytosine levels by screening mutagenized populations for individuals that have reduced restriction site modification. Three of these mutations define a novel locus, DDM1, important for maintenance of genomic DNA methylation patterns. Loss of function alleles at the DDM1 locus lead to an immediate depletion of cytosine methylation in the repetitive DNA component of the genome and a slow loss of methylation in low-copy sequences. In parallel with the loss of low-copy DNA methylation, ddm1 mutants accumulate epigenetic alterations at a limited number of loci which result in developmental abnormalities. We are currently investigating the molecular basis of the epigenetic alterations. Our findings to date support the view that DNA methylation plays an important role in cementing inherited epigenetic gene expression states. We have recently isolated the DDM1 gene, which encodes a protein with significant similarity proteins involved in chromatin remodeling in other organisms. Investigation of the interaction between chromatin and the DNA methylation system will form a major focus of the labıs efforts. An additional project in the lab concerns the characterization of a higher eukaryotic centromere.
Jeddeloh, J.A., Bender, J., and Richards, E.J. (1998) The DNA methylation locus DDM1 is required for maintenance of gene silencing in Arabidopsis. Genes Dev. 12:1714-1725.
Richards, E.J., and Dawe, K. (1998) Plant centromeres: structure and control. Curr. Opin. Plant Biol. 1:130-135.
Round, E., Flowers, S.K., and Richards, E.J. (1997) Arabidopsis thaliana centromere regions: Genetic map positions and repetitive DNA structure. Genome Research 7:1045-1053.
Richards, E.J. (1997) DNA methylation and plant development. Trends Genet. 13:293-341.
Kakutani, T., Jeddeloh, J.A., Flowers, S. , Munakata, K., and Richards, E.J. (1996) Developmental abnormalities and epimutations associated with DNA hypomethylation mutations. Proc. Natl. Acad. Sci. USA 93:12406-12411.
Jeddeloh, J.A., and Richards, E.J. (1996) mCCG methylation in angiosperms. Plant Journal 9:579-586.
Richards, E.J. (1995). Plant Telomeres. In Telomeres (eds. C. Greider, and E.H. Blackburn). Cold Spring Harbor Laboratory Press, Cold Spring Harbor.
Martienssen, R.A., and Richards, E.J. (1995) DNA methylation in eukaryotes. Curr. Opin. Gen. Dev. 5:234-242.
Kakutani, T., Jeddeloh, J.A., and Richards, E.J. (1995) Characterization of an Arabidopsis thaliana DNA hypomethylation mutant. Nucleic Acids Res. 23:130-137.
Richards, E.J., Vongs, A., Walsh, M., Yang, J., and Chao, S. (1993) Substructure of telomere repeat arrays. In The Chromosome (eds. J.S. Heslop-Harrison and R.B. Flavell). Bios Scientific Publishers, Oxford.
Vongs, A., Kakutani, T., Martienssen, R., and Richards, E.J. (1993) Arabidopsis thaliana DNA methylation mutants. Science 260:1926-1928.
Richards, E.J., Chao, S., Vongs, A., and Yang, J. (1992) Characterization of Arabidopsis thaliana telomeres isolated in yeast. Nucleic Acids Res. 20:4039-4046.
Richards, E.J., Goodman, H.M., and Ausubel, F.M. (1991) The centromere region of Arabidopsis thaliana chromosome1 contains telomere-similar sequences. Nucleic Acids Res. 19:3351-3357.
Richards, E.J., and Ausubel, F.M. (1988) Isolation of a higher eukaryotic
telomere from Arabidopsis thaliana. Cell 53:127-136.
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