It’s time to welcome a new DNA modification to the epigenetic jungle! A collection of more than seventeen modifications have been spotted in the wilds of genomic DNA; however, only the biological effects of the prevalent 5-methyldeoxycytosine (5mC) (and its oxidated family members), along with N6-methyldeoxyadenosine (6mA) have been explored in any depth. Do other modifications exist unseen in the wild, and just what roles do they play?
Acetylation of the N4 position of cytosine represents a highly-conserved modification of ribosomal and transfer RNA and eukaryotic mRNA, where it promotes stability and translational efficiency. As RNA modifications often have direct DNA analogs, adventurers led by Yufeng Wu (Nanjing Agricultural University, China) explored the existence and function of N4-acetyldeoxycytosine (4acC)-modified genomic DNA from the model plant Arabidopsis thaliana.
Let’s join Wang and colleagues on their vine-swinging adventure through the epigenetic jungle, where they describe a new DNA modification in plants:
- 4acC immunoprecipitation followed by sequencing (4acC-IP-seq) reveals the general abundance of 4acC and its association with euchromatic regions and presence at half of expressed protein-coding genes
- 4acC locates to transcription start sites and associates with actively transcribed genes
- 4acC and 5mC occupy distinct genomic regions, and changes in 5mC levels do not directly alter 4acC distribution; however, these DNA modifications may combinatorically contribute to gene expression
- Genes marked with 4acC possess higher 5mC methylation density in a CG context within gene bodies but lower methylation levels in CHG and CHH (H being A or T) contexts compared to genes lacking 4acC
- 4acC colocalizes with permissive histone modifications (such as H3K4me2/3, H3K36me3, and H3K14ac), which display a dominant effect over 4acC when it comes to gene expression
- However, 4acC associates with gene expression in the absence of permissive histone modifications or the presence of repressive histone modifications
- Mass spectrometry-based evaluations demonstrate the existence of the 4acC modification in the genomic DNA of other plants (i.e., rice and maize) but also in mouse and human cells, which suggests the existence of similar epigenetic modification systems in distinct species
The authors bring some welcome discoveries on returning from their adventures through the epigenetic jungle of Arabidopsis DNA – the identification of N4-acetyldeoxycytosine as a new DNA modification in higher eukaryotes that may impact gene expression. Where to next for these epigenetic adventurers, we hear you ask? Subsequent expeditions into the wilds of genomic DNA will aim to reveal the acetyltransferase enzyme that mediates the N4-acetyldeoxycytosine modification, investigate the regulatory role of N4-acetyldeoxycytosine in gene expression, and discover any crosstalk with other epigenetic mechanisms.
Make a path through the epigenetic jungle and discover more at Genome Biology, January 2022.