A DNA methylation reader complex that enhances gene transcription

Abstract

DNA methylation generally functions as a repressive transcriptional signal, but it is also known to activate gene expression. In either case, the downstream factors remain largely unknown. By using comparative interactomics, we isolated proteins in Arabidopsis thaliana that associate with methylated DNA. Two SU(VAR)3–9 homologs, the transcriptional anti-silencing factor SUVH1, and SUVH3, were among the methyl reader candidates. SUVH1 and SUVH3 bound methylated DNA in vitro, were associated with euchromatic methylation in vivo, and formed a complex with two DNAJ domain-containing homologs, DNAJ1 and DNAJ2. Ectopic recruitment of DNAJ1 enhanced gene transcription in plants, yeast, and mammals. Thus, the SUVH proteins bind to methylated DNA and recruit the DNAJ proteins to enhance proximal gene expression, thereby counteracting the repressive effects of transposon insertion near genes.

A methylated‐DNA‐binding complex required for plant development mediates transcriptional activation of promoter methylated genes

“…We noted that a similar study was recently published online when we were preparing our paper (Harris et al 2018). The published study reported that SUVH1 and SUVH3 interact with DNAJ1 and DNAJ2 (which are corresponding to SDJ1 and SDJ2, respectively, in our study) and thus form a complex that enhances gene transcription; the main conclusions reported in the published study are confirmed by our independent study.…”

A group of SUVH methyl‐DNA binding proteins regulate expression of the DNA demethylase ROS1 in Arabidopsis

“…These three DnaJ‐domain proteins were also pulled down, along with SUVH3 and SUVH1 in a DNA‐trap experiment using methylated MEMS as a probe, wiht unmethylated MEMS as a control (Figure B). During the preparation of this manuscript, Harris and colleagues also identified SUVH1, SUVH3 and DnaJ proteins as components of a DNA methylation reader complex that activates gene expression (Harris et al ). It is interesting to note that in this issue of the Journal , Zhao and colleagues show SUVH1 and SUVH3 function synergistically with these DnaJ proteins to prevent promoter methylated genes from silencing (Zhao et al ).…”

A SUVH‐DNAJ/SDJ protein complex activates the expression of promoter‐methylated genes in Arabidopsis

“…However, Xiao et al found 1674 hyper‐methylated regions (HMRs) in suvh1/3/7/8 quadruple mutant compared to Col‐0. Interestingly, in all of the three studies, they observed reduced ROS1 expression in suvh1/3 , sdj1/2 , and sdj 1/2/3 mutants (Harris et al ; Xiao et al ; Zhao et al ). Reduced ROS1 expression is usually associated with increase of DNA methylation at ROS1 target loci.…”

“…This protein complex regulates ROS1 expression through binding to the methylated MEMS sequence that is known to be guided by the RdDM pathway (Lei et al ). The regulation of ROS1 expression by the SUVH‐SDJ complex was confirmed by whole‐genome chromatin immunoprecipitation assay sequencing and RNA‐seq analyses (Harris et al ; Zhao et al 2019). In the study of Xinjian He's group, they found that SUVH‐SDJ protein complex can also bind many other highly methylated genomic regions, which are predominantly methylated by the RdDM pathway.…”

“…These studies suggest that SUVHs promote gene expression without altering DNA methylation at binding loci, and SUVHs function down‐stream of DNA methylation (Li et al ; Harris et al ; Xiao et al ; Zhao et al ). Zhao et al () found that DNA methylation level was not disturbed in suvh1/3 and sdj1/2/3 mutants.…”