title: DNA demethylases target promoter transposable elements to positively regulate stress responsive genes in Arabidopsis.
abstract: BACKGROUND
  DNA demethylases regulate DNA methylation levels in eukaryotes. Arabidopsis encodes four DNA demethylases, DEMETER (DME), REPRESSOR OF SILENCING 1 (ROS1), DEMETER-LIKE 2 (DML2), and DML3. While DME is involved in maternal specific gene expression during seed development, the biological function of the remaining DNA demethylases remains unclear.
  
  
  RESULTS
  We show that ROS1, DML2, and DML3 play a role in fungal disease resistance in Arabidopsis. A triple DNA demethylase mutant, rdd (ros1 dml2 dml3), shows increased susceptibility to the fungal pathogen Fusarium oxysporum. We identify 348 genes differentially expressed in rdd relative to wild type, and a significant proportion of these genes are downregulated in rdd and have functions in stress response, suggesting that DNA demethylases maintain or positively regulate the expression of stress response genes required for F. oxysporum resistance. The rdd-downregulated stress response genes are enriched for short transposable element sequences in their promoters. Many of these transposable elements and their surrounding sequences show localized DNA methylation changes in rdd, and a general reduction in CHH methylation, suggesting that RNA-directed DNA methylation (RdDM), responsible for CHH methylation, may participate in DNA demethylase-mediated regulation of stress response genes. Many of the rdd-downregulated stress response genes are downregulated in the RdDM mutants nrpd1 and nrpe1, and the RdDM mutants nrpe1 and ago4 show enhanced susceptibility to F. oxysporum infection.
  
  
  CONCLUSIONS
  Our results suggest that a primary function of DNA demethylases in plants is to regulate the expression of stress response genes by targeting promoter transposable element sequences.
authors.forename: Tuan-Ngoc
authors.initials: TN
authors.lastname: Le
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schumann
authors.forename: Neil A
authors.initials: NA
authors.lastname: Smith
authors.forename: Sameer
authors.initials: S
authors.lastname: Tiwari
authors.forename: Phil Chi Khang
authors.initials: PC
authors.lastname: Au
authors.forename: Qian-Hao
authors.initials: QH
authors.lastname: Zhu
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Taylor
authors.forename: Kemal
authors.initials: K
authors.lastname: Kazan
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Llewellyn
authors.forename: Ren
authors.initials: R
authors.lastname: Zhang
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Dennis
authors.forename: Ming-Bo
authors.initials: MB
authors.lastname: Wang
mesh_terms: D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004251:DNA Transposable Elements; D060467:Disease Resistance; D005670:Fusarium / Q000502:physiology; D015870:Gene Expression; D018506:Gene Expression Regulation, Plant; D055786:Gene Knockout Techniques; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010935:Plant Diseases / Q000382:microbiology; D011401:Promoter Regions, Genetic; D013312:Stress, Physiological
chemical_list: D029681:Arabidopsis Proteins; D004251:DNA Transposable Elements; D009687:Nuclear Proteins; C471271:ROS1 protein, Arabidopsis; C519856:DML2 protein, Arabidopsis; C519857:DML3 protein, Arabidopsis; D045647:DNA Glycosylases