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MET18 Connects the Cytosolic Iron-Sulfur Cluster Assembly Pathway to Active DNA Demethylation in


DNA cytosine methylation is a major epigenetic mark that confers transcriptional regulation. Active removal of DNA methylation is important for plants and mammals during development and in responses to various stress conditions. In the model plant species Arabidopsis thaliana, active DNA demethylation depends on a family of 5-methylcytosine DNA glycosylases/demethylases including ROS1, DME, and others. While the epigenetic function of this demethylase family is well-known, little is known about how their enzymatic activities may be regulated. In this report, we carried out a forward genetic screen for anti-silencing factors and identified MET18, a conserved component of cytosolic iron-sulfur cluster assembly (CIA) pathway in eukaryotes, as being required for the ROS1-dependent active DNA demethylation. Dysfunction of MET18 causes DNA hyper-methylation at thousands of genomic loci where DNA methylation is pruned by ROS1. In addition, ROS1 physically interacts with MET18 and other CIA pathway components; while a conserved iron-sulfur-binding motif is indispensable for ROS1 enzyme activity. Our results suggested that MET18 affects DNA demethylation by influencing ROS1 enzymatic activity via direct interaction with the iron-sulfur-binding motif of ROS1, highlighting a direct connection between iron-sulfur cluster assembly and active DNA demethylation.


Vyšlo v časopise: MET18 Connects the Cytosolic Iron-Sulfur Cluster Assembly Pathway to Active DNA Demethylation in. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005559
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005559

Souhrn

DNA cytosine methylation is a major epigenetic mark that confers transcriptional regulation. Active removal of DNA methylation is important for plants and mammals during development and in responses to various stress conditions. In the model plant species Arabidopsis thaliana, active DNA demethylation depends on a family of 5-methylcytosine DNA glycosylases/demethylases including ROS1, DME, and others. While the epigenetic function of this demethylase family is well-known, little is known about how their enzymatic activities may be regulated. In this report, we carried out a forward genetic screen for anti-silencing factors and identified MET18, a conserved component of cytosolic iron-sulfur cluster assembly (CIA) pathway in eukaryotes, as being required for the ROS1-dependent active DNA demethylation. Dysfunction of MET18 causes DNA hyper-methylation at thousands of genomic loci where DNA methylation is pruned by ROS1. In addition, ROS1 physically interacts with MET18 and other CIA pathway components; while a conserved iron-sulfur-binding motif is indispensable for ROS1 enzyme activity. Our results suggested that MET18 affects DNA demethylation by influencing ROS1 enzymatic activity via direct interaction with the iron-sulfur-binding motif of ROS1, highlighting a direct connection between iron-sulfur cluster assembly and active DNA demethylation.


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