N6-Methyldeoxyadenosine Marks Active Transcription Start Sites in Chlamydomonas

Abstract

SUMMARY N6-methyldeoxyadenosine (6mA or m6A) is a DNA modification preserved in prokaryotes to eukaryotes. It is widespread in bacteria, and functions in DNA mismatch repair, chromosome segregation, and virulence regulation. In contrast, the distribution and function of 6mA in eukaryotes have been unclear. Here we present a comprehensive analysis of the 6mA landscape in the genome of Chlamydomonas using new sequencing approaches. We identified the 6mA modification in 84% of genes in Chlamydomonas. We found that 6mA mainly locates at ApT dinucleotides around transcription start sites (TSS) with a bimodal distribution, and appears to mark active genes. A periodic pattern of 6mA deposition was also observed at base resolution, which is associated with nucleosome distribution near the TSS, suggesting a possible role in nucleosome positioning. The new genome-wide mapping of 6mA and its unique distribution in the Chlamydomonas genome suggest potential regulatory roles of 6mA in gene expression in eukaryotic organisms.

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

“…2), suggesting that one or more of these enzymes probably generate the observed m 6 A. The chlorophyte Chlamydomonas was reported as having 0.5% of its adenines methylated 24, 36, 52. A recent study has provided exquisite detail on its methylome 52: the bulk of the m 6 A is associated with specific motifs centered on an AT dinucleotide (one third of them mapping to motifs CATG and GATC), with a bimodal distribution around the transcription start site.…”

“…The m 6 A methylomes are very different in the three models in which they have been determined 52, 53, 54. Hence, despite common features of m 6 A modifications in distantly related eukaryotes, there are likely to be functional differences that are currently poorly understood.…”

“…3). This suggests that methylation of both DNA and (pre)mRNA, including perhaps chloroplast transcripts, is likely to be important for the regulation of physiology in microbial algae 52.…”

Widespread adenine N6-methylation of active genes in fungi

“…However, genomic 6mA has recently been demonstrated to play crucial roles in both gene and transposon regulation, where it either (i) suppresses expression of transposable elements in animals during development [2][3][4] or (ii) is associated with promoters of actively expressed genes and is involved in nucleosome positioning in algae 1 . These studies demonstrate that while 6mA is present in eukaryotes, it may serve distinct genomic functions across diverse phylogenetic groups.…”

A new twist on epigenetics

“…"I almost fell to the floor, " He says. In April 2015, the three papers came out simultaneously in Cell [10][11][12] .…”