Steven E. Jacobsen
University of California, Los Angeles
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Primary Section: 62, Plant, Soil, and Microbial Sciences Secondary Section: 25, Plant Biology Membership Type:
Member
(elected 2011)
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Research Interests
My laboratory uses genetic and genomic techniques to study epigenetic gene silencing in the model plant Arabidopsis thaliana. We found that the initiation of DNA methylation requires the DNA methyltransferase DRM2, a homolog of mammalian Dnmt3, which is guided by 24 nucleotide small RNAs and several RNA silencing proteins including Pol IV, RDR2, DCL3, Pol V, and AGO4. The mechanisms involved in the maintenance of preexisting DNA methylation are different for methylation in the three different sequence contexts, CG, CHG and CHH. CG methylation is coupled with DNA replication and requires the DNA methyltransferase MET1, a homolog of mammalian Dnmt1, and the accessory factor VIM1, a homolog of mammalian UHRF1. CHG methylation is inherited by a positive feedback loop between histone H3K9 methylation and CHG DNA methylation, because the H3K9 methyltransferase KRYPTONITE binds directly to CHG methylated DNA, and the CHG DNA methyltransferase CMT3 binds directly to methylated histone H3 tails. CHH methylation is maintained by continual targeting of DRM2 and small RNAs to particular loci. Other work suggest that DNA methylation not only serves as a mark of gene silencing, but also acts to regulate the DNA replication of transposable elements.
