N4-acetyldeoxycytosine DNA modification marks euchromatin regions in Arabidopsis thaliana

Abstract

Background Direct analogs of chemically modified bases that carry important epigenetic information, such as 5-methylcytosine (m5C)/5-methyldeoxycytosine (5mC), 5-hydroxymethylcytosine (hm5C)/5-hydroxymethyldeoxycytosine (5hmC), and N6-methyladenosine (m6A)/N6-methyldeoxyadenosine (6mA), are detected in both RNA and DNA, respectively. The modified base N4-acetylcytosine (ac4C) is well studied in RNAs, but its presence and epigenetic roles in cellular DNA have not been explored. Results Here, we demonstrate the existence of N4-acetyldeoxycytosine (4acC) in genomic DNA of Arabidopsis with multiple detection methods. Genome-wide profiling of 4acC modification reveals that 4acC peaks are mostly distributed in euchromatin regions and present in nearly half of the expressed protein-coding genes in Arabidopsis. 4acC is mainly located around transcription start sites and positively correlates with gene expression levels. Imbalance of 5mC does not directly affect 4acC modification. We also characterize the associations of 4acC with 5mC and histone modifications that cooperatively regulate gene expression. Moreover, 4acC is also detected in genomic DNA of rice, maize, mouse, and human by mass spectrometry. Conclusions Our findings reveal 4acC as a hitherto unknown DNA modification in higher eukaryotes. We identify potential interactions of this mark with other epigenetic marks in gene expression regulation.

NAT10 acetylates BCL-XL mRNA to promote the proliferation of multiple myeloma cells through PI3K-AKT pathway

“…It also can improve translation efficiency and stability of mRNA. A recent study demonstrates that ac4C on tRNA in plants can improve translation efficiency and fidelity ( 27 ), while ac4C plays an important role in maintaining the stability of tRNA that is associated with the high thermotolerance of cells ( 28 ). The ac4C is involved in the occurrence of various diseases including cancer ( 6 ), inflammation ( 29 ), metabolic diseases ( 30 ), autoimmune diseases ( 31 ).…”

Shaping eukaryotic epigenetic systems by horizontal gene transfer

“…More exotic DNA modifications in addition to the bacterial "big three" are being reported, although the enzymatic basis for their deposition has not always been elucidated. [125][126][127] Identification of the corresponding enzymes capable of adding such modifications should achieve highest priority in future studies exploring unconventional epigenetic systems across the eukaryotic tree of life.…”

From correlation to causation: The new frontier of transgenerational epigenetic inheritance

“…[36] It is still not understood how some of these regions can escape reprogramming but DNA methylation seems to be a robust transgenerational epigenetic factor in systems that possess it. Beyond 5mC there are other DNA methylation events, such as N6-methyladenosine [37] and N4-methylcytosine [38] and other modifications to DNA, including N4-acetylcytosine [39] and…”

“…[ 36 ] It is still not understood how some of these regions can escape reprogramming but DNA methylation seems to be a robust transgenerational epigenetic factor in systems that possess it. Beyond 5mC there are other DNA methylation events, such as N6‐methyladenosine [ 37 ] and N4‐methylcytosine [ 38 ] and other modifications to DNA, including N4‐acetylcytosine [ 39 ] and 5‐hydoxymethyluracil, [ 40 ] which could each play a role in transmitting non‐genetic information across generations. Having a deeper mechanistic understanding of these additional modifications could help reveal whether these rarer DNA modifications could play a role specifically in the inheritance of non‐genetic information.…”