MTHFD1 controls DNA methylation in Arabidopsis

Martin Groth (), Guillaume Moissiard, Markus Wirtz, Haifeng Wang, Carolina Garcia-Salinas, Perla A. Ramos-Parra, Sylvain Bischof, Suhua Feng, Shawn J. Cokus, Amala John, Danielle C. Smith, Jixian Zhai, Christopher J. Hale, Jeff A. Long, Ruediger Hell, Rocío I. Díaz de la Garza and Steven E. Jacobsen ()
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Martin Groth: Cell, and Developmental Biology, University of California Los Angeles
Guillaume Moissiard: Cell, and Developmental Biology, University of California Los Angeles
Markus Wirtz: Centre for Organismal Studies, University of Heidelberg
Haifeng Wang: Basic Forestry and Proteomics Research Center, Haixia Institute of Science and Technology (HIST), Fujian Province Key Laboratory of Plant Virology, Institute of Plant Virology, Fujian Agriculture and Forestry University
Carolina Garcia-Salinas: Tecnologico de Monterrey, Campus Monterrey
Perla A. Ramos-Parra: Tecnologico de Monterrey, Campus Monterrey
Sylvain Bischof: Cell, and Developmental Biology, University of California Los Angeles
Suhua Feng: Cell, and Developmental Biology, University of California Los Angeles
Shawn J. Cokus: Cell, and Developmental Biology, University of California Los Angeles
Amala John: Cell, and Developmental Biology, University of California Los Angeles
Danielle C. Smith: Cell, and Developmental Biology, University of California Los Angeles
Jixian Zhai: Cell, and Developmental Biology, University of California Los Angeles
Christopher J. Hale: Cell, and Developmental Biology, University of California Los Angeles
Jeff A. Long: Cell, and Developmental Biology, University of California Los Angeles
Ruediger Hell: Centre for Organismal Studies, University of Heidelberg
Rocío I. Díaz de la Garza: Tecnologico de Monterrey, Campus Monterrey
Steven E. Jacobsen: Cell, and Developmental Biology, University of California Los Angeles

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract DNA methylation is an epigenetic mechanism that has important functions in transcriptional silencing and is associated with repressive histone methylation (H3K9me). To further investigate silencing mechanisms, we screened a mutagenized Arabidopsis thaliana population for expression of SDCpro-GFP, redundantly controlled by DNA methyltransferases DRM2 and CMT3. Here, we identify the hypomorphic mutant mthfd1-1, carrying a mutation (R175Q) in the cytoplasmic bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (MTHFD1). Decreased levels of oxidized tetrahydrofolates in mthfd1-1 and lethality of loss-of-function demonstrate the essential enzymatic role of MTHFD1 in Arabidopsis. Accumulation of homocysteine and S-adenosylhomocysteine, genome-wide DNA hypomethylation, loss of H3K9me and transposon derepression indicate that S-adenosylmethionine-dependent transmethylation is inhibited in mthfd1-1. Comparative analysis of DNA methylation revealed that the CMT3 and CMT2 pathways involving positive feedback with H3K9me are mostly affected. Our work highlights the sensitivity of epigenetic networks to one-carbon metabolism due to their common S-adenosylmethionine-dependent transmethylation and has implications for human MTHFD1-associated diseases.

Date: 2016
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DOI: 10.1038/ncomms11640

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