Gene Body Methylation in Plants: Mechanisms, Functions, and Important Implications for Understanding Evolutionary Processes

Abstract

Gene body methylation (gbM) is an epigenetic mark where gene exons are methylated in the CG context only, as opposed to CHG and CHH contexts (where H stands for A, C or T). CG methylation is transmitted transgenerationally in plants, opening the possibility that gbM may be shaped by adaptation. This presupposes, however, that gbM has a function that affects phenotype, which has been a topic of debate in the literature. Here we review our current knowledge of gbM in plants. We start by presenting the well elucidated mechanisms of plant gbM establishment and maintenance. We then review more controversial topics: the evolution of gbM and the potential selective pressures that act on it. Finally, we discuss the potential functions of gbM that may affect organismal phenotypes: gene expression stabilization and upregulation, inhibition of aberrant transcription (reverse and internal), prevention of aberrant intron retention and protection against TE insertions. To bolster the review of these topics, we include novel analyses to assess the effect of gbM on transcripts. Overall, a growing body of literature finds that gbM correlates with levels and patterns of gene expression. It is not clear, however, if this is a causal relationship. Altogether, functional work suggests that the effects of gbM, if any, must be relatively small, but there is nonetheless evidence that it is shaped by natural selection. We conclude by discussing the potential adaptive character of gbM and its implications for an updated view of the mechanisms of adaptation in plants.

Unified establishment and epigenetic inheritance of DNA methylation through cooperative MET1 activity

“…Flowering plants and most invertebrates have a type of intragenic methylation, called gene body methylation (gbM), that is distinct from TE methylation (Muyle et al, 2022). GbM tends to occur in exonic nucleosomes of conserved, constitutively expressed genes (Chodavarapu et al, 2010; Feng et al, 2010; Lewis et al, 2020; Zemach et al, 2010), and can prevent aberrant intragenic transcription and promote gene expression in Arabidopsis (Choi et al, 2020; Shahzad et al, 2021).…”

“…GbM tends to occur in exonic nucleosomes of conserved, constitutively expressed genes (Chodavarapu et al, 2010; Feng et al, 2010; Lewis et al, 2020; Zemach et al, 2010), and can prevent aberrant intragenic transcription and promote gene expression in Arabidopsis (Choi et al, 2020; Shahzad et al, 2021). Compared to TE methylation, the epigenetics of gbM are far more mysterious (Muyle et al, 2022). GbM is characterized by the absence of non-CG methylation (the type catalyzed by the DRM and CMT enzymes) (Takuno & Gaut, 2012; Zemach & Zilberman, 2010) and by a more equal balance between the rates of mCG loss and gain (van der Graaf et al, 2015).…”

Environmental response in gene expression and DNA methylation reveals factors influencing the adaptive potential ofArabidopsis lyrata

“…For example, as histone modifications are known to exert a major influence on gene expression (Lloyd and Lister, 2022), future work studying environmental induction of histone modifications in natural conditions holds promise to expand our understanding of the evolutionary consequences of epigenome plasticity (Husby, 2022). In any case, we discovered greater than expected overlap between genes that were differentially expressed and methylated between the populations, suggesting that changes in DNA methylation, when they accumulate over generations, may influence patterns of gene expression (Muyle et al, 2022;Takuno et al, 2017).…”

“…We also used logistic regression and LRTs to conduct a similar analysis among differentially methylated genes (DMGs). As genic methylation can have distinct effects on gene expression depending on the sequence context (Muyle et al, 2022), we searched for DMGs using CG and non-CG methylation separately.…”

Transgressive and parental dominant gene expression and cytosine methylation during seed development inBrassica napushybrids

“…Epigenomic features, those resulting into phenotypical changes without alterations in DNA sequences, include chromatin interaction, histone modification and DNA methylation (Fitz-James and Cavalli, 2022). Genome-wide methylation analyses have found methylation level differences across plant species and determined phenotypic consequences as a result of genomic methylation (Bartels et al, 2018; Muyle et al, 2022).…”