Linking epigenetic function to electrostatics: The DNMT2 structural model example

Abstract

The amino acid sequence of DNMT2 is very similar to the catalytic domains of bacterial and eukaryotic proteins. However, there is great variability in the region of recognition of the target sequence. While bacterial DNMT2 acts as a DNA methyltransferase, previous studies have indicated low DNA methylation activity in eukaryotic DNMT2, with preference by tRNA methylation. Drosophilids are known as DNMT2-only species and the DNA methylation phenomenon is a not elucidated case yet, as well as the ontogenetic and physiologic importance of DNMT2 for this species group. In addition, more recently study showed that methylation in the genome in Drosophila melanogaster is independent in relation to DNMT2. Despite these findings, Drosophilidae family has more than 4,200 species with great ecological diversity and historical evolution, thus we, therefore, aimed to examine the drosophilids DNMT2 in order to verify its conservation at the physicochemical and structural levels in a functional context. We examined the twenty-six DNMT2 models generated by molecular modelling and five crystallographic structures deposited in the Protein Data Bank (PDB) using different approaches. Our results showed that despite sequence and structural similarity between species close related, we found outstanding differences when they are analyzed in the context of surface distribution of electrostatic properties. The differences found in the electrostatic potentials may be linked with different affinities and processivity of DNMT2 for its different substrates (DNA, RNA or tRNA) and even for interactions with other proteins involved in the epigenetic mechanisms.

Genome-wide investigation and transcriptional analysis of cytosine-5 DNA methyltransferase and DNA demethylase gene families in tea plant (Camellia sinensis) under abiotic stress and withering processing

“…DNMT2 is the smallest MET gene family found in different eukaryotes. Due to the considerable variability in the specific target recognition domain, DNMT2 is also involved in RNA methylation modification (Jeltsch et al, 2017;Vieira et al, 2017). DRM is homologous to DNMT3 in mammals, and both differ only in the order of related catalytic domains (Cao et al, 2000).…”

Identification and characterization of the cytosine-5 DNA methyltransferase gene family inSalvia miltiorrhiza

“…The function of SmCMT2a remains to be elucidated. Although DNMT2 contains highly conserved C-terminal methyltransferase domain and is able to interact with type-2 histone deacetylases (AtHD2s) in Arabidopsis ( Song et al, 2010 ), its function remains largely unclear ( Goll et al, 2006 ; Ponger & Li, 2005 ; Vieira et al, 2017 ). In this study, we found that SmDNMT2 showed no differential transcript abundance in all tissues analyzed and various treatments ( Figs.…”

Genome-wide Identification and Transcriptional Characterization of Dna Methyltransferases Conferring Temperature-sensitive Male Sterility in Wheat

“…Some studies have shown that the absence of DNA-methylase domain makes the DMT proteins can't normally methylate the cytosine [6,67]. All members of TaDRM (27) and TaDNMT2 (3) only contained the DNAmethylase domain. The BAH domain (Bromo Adjacent Homology) existed in almost members of TaMET1 and TaCMT.…”

“…Based on sequence homology, the DNMT2 was originally considered to be DNA methyltransferase. However, robust DNA methyltransferase activity could not be observed using DNMT2 preparations and the considerable variability in the target DNA sequences showed that DNMT2 enzymes were actually tRNA transferases [27][28][29].…”