Abstract
BackgroundChromatin organizes DNA and regulates its transcriptional activity through epigenetic modifications. Heterochromatic regions of the genome are generally transcriptionally silent, while euchromatin is more prone to transcription. During DNA replication, both genetic information and chromatin modifications must be faithfully passed on to daughter strands. There is evidence that DNA polymerases play a role in transcriptional silencing, but the extent of their contribution and how it relates to heterochromatin maintenance is unclear.ResultsWe isolate a strong hypomorphic Arabidopsis thaliana mutant of the POL2A catalytic subunit of DNA polymerase epsilon and show that POL2A is required to stabilize heterochromatin silencing genome-wide, likely by preventing replicative stress. We reveal that POL2A inhibits DNA methylation and histone H3 lysine 9 methylation. Hence, the release of heterochromatin silencing in POL2A-deficient mutants paradoxically occurs in a chromatin context of increased levels of these two repressive epigenetic marks. At the nuclear level, the POL2A defect is associated with fragmentation of heterochromatin.ConclusionThese results indicate that POL2A is critical to heterochromatin structure and function, and that unhindered replisome progression is required for the faithful propagation of DNA methylation throughout the cell cycle.
Highlights
Chromatin organizes DNA and regulates its transcriptional activity through epigenetic modifications
POL2A maintains gene silencing genome-wide Certain transgenes can spontaneously undergo silencing, which is subsequently maintained by mechanisms identical to those controlling silencing of endogenous transposable elements (TEs) and genes
The anx2 plant phenotype closely resembled that of mutants of the POL2A gene, which encodes the catalytic subunit of the DNA Pol ε responsible for most of the leading strand elongation during eukaryotic DNA replication (Additional file 1: Figure S1A) [15, 36, 37]
Summary
Chromatin organizes DNA and regulates its transcriptional activity through epigenetic modifications. Bourguet et al Genome Biology (2020) 21:283 can be distinguished in cell nuclei: euchromatin, which contains most genes and is loosely compacted, and heterochromatin, which is enriched in repetitive DNA, genepoor, and highly compacted These two main chromatin states associate with distinct patterns of so-called epigenetic marks, namely DNA cytosine methylation and posttranslational modification of histone proteins, which influence gene activity in a DNA sequence-independent manner. H3K9me recruits CHROMOMETHYLASE 2 (CMT2), which is responsible for the maintenance of most genomic asymmetric CHH methylation, and function partially redundantly with CMT3 to methylate CHG sites [2, 3] It is currently unknown whether CMT2 activity is linked to DNA replication. The histone H2A variant H2A.W incorporates into Arabidopsis heterochromatin, independently of DNA and H3K9 methylation [6]
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