Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, CZ-612 65, Brno, Czech Republic.
Chromosome Res. 2019 Mar;27(1-2):41-55. doi: 10.1007/s10577-018-9596-x. Epub 2019 Jan 4.
Repair of ribosomal DNA (rDNA) is a very important nuclear process due to the most active transcription of ribosomal genes. Proper repair of rDNA is required for physiological biogenesis of ribosomes. Here, we analyzed the epigenetics of the DNA damage response in a nucleolar compartment, thus in the ribosomal genes studied in nonirradiated and UVA-irradiated mouse embryonic fibroblasts (MEFs). We found that the promoter of ribosomal genes is not abundant on H4K20me2, but it is densely occupied by H4K20me3. Ribosomal genes, regulated via UBF1/2 proteins, were characterized by an interaction between UBF1/2 and H4K20me2/me3. This interaction was strengthened by UVA irradiation that additionally causes a focal accumulation of H4K20me3 in the nucleolus. No interaction has been found between UBF1/2 and H3K9me3. Interestingly, UVA irradiation decreases the levels of H3K9me3 and H4K20me3 at 28S rDNA. Altogether, the UVA light affects the epigenetic status of ribosomal genes at 28S rDNA and strengthens an interaction between UBF1/2 proteins and H4K20me2/me3.
核糖体 DNA（rDNA）的修复是一个非常重要的核过程，因为核糖体基因的转录最为活跃。rDNA 的正确修复对于核糖体的生理生物发生是必需的。在这里，我们分析了核仁隔室中 DNA 损伤反应的表观遗传学，即在未辐照和 UVA 辐照的小鼠胚胎成纤维细胞（MEFs）中研究的核糖体基因。我们发现，核糖体基因的启动子上 H4K20me2 不丰富，但它被 H4K20me3 密集占据。受 UBF1/2 蛋白调节的核糖体基因的特征是 UBF1/2 与 H4K20me2/me3 之间的相互作用。UVA 照射会增强这种相互作用，此外还会导致核仁中 H4K20me3 的局灶性积累。尚未发现 UBF1/2 与 H3K9me3 之间存在相互作用。有趣的是，UVA 照射会降低 28S rDNA 处的 H3K9me3 和 H4K20me3 水平。总的来说，UVA 光会影响 28S rDNA 处核糖体基因的表观遗传学状态，并增强 UBF1/2 蛋白与 H4K20me2/me3 之间的相互作用。
