RT Journal Article
SR Electronic
T1 Dynamic DNA methylation turnover in gene bodies is associated with enhanced gene expression plasticity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.12.02.518885
DO 10.1101/2022.12.02.518885
A1 Clara J. Williams
A1 Dawei Dai
A1 Kevin A. Tran
A1 J. Grey Monroe
A1 Ben P. Williams
YR 2022
UL http://biorxiv.org/content/early/2022/12/03/2022.12.02.518885.abstract
AB Background In diverse eukaryotes, DNA methylation is deposited within the coding regions of many genes, termed gene body methylation (GbM). Whereas the role of DNA methylation on the silencing of transposons and repetitive DNA is well understood, gene body methylation is not associated with transcriptional repression, and its biological importance has remained unclear.Results We report a newly discovered type of GbM in plants, which is under constitutive addition and removal by dynamic methylation modifiers in all cells, including the germline. Methylation at Dynamic GbM genes is removed by the DRDD demethylation pathway, and added by an unknown source of de novo methylation, most likely the maintenance methyltransferase MET1. We show that the Dynamic GbM state is present at homologous genes across divergent lineages (>100 million years), indicating evolutionary conservation. Furthermore, we demonstrate that Dynamic GbM is tightly associated with the presence of a promoter/regulatory chromatin state within the gene body, in contrast to other gene body methylated genes. Lastly, we find Dynamic GbM is associated with enhanced gene expression plasticity across development and diverse physiological conditions, whereas stably methylated GbM genes exhibit reduced plasticity.Conclusions This study proposes a new model for GbM in regulating gene expression plasticity, including a newly discovered type of GbM in which increased gene expression plasticity is associated with the activity of DNA methylation writers and erasers and the enrichment of a regulatory chromatin state. We propose that Dynamic GbM is a hallmark of genes that can navigate a greater landscape of transcriptional states by maintaining regulatory flexibility.Competing Interest StatementThe authors have declared no competing interest.