University of Göttingen, Göttingen Center for Molecular Biosciences, Department of Developmental Biology, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.
Max Planck Institute for Multidisciplinary Sciences, Department for Molecular Developmental Biology, Am Fassberg 11, 37077 Göttingen, Germany.
Sci Adv. 2023 Feb 3;9(5):eadd6440. doi: 10.1126/sciadv.add6440. Epub 2023 Feb 1.
Epigenetic inheritance during DNA replication requires an orchestrated assembly of nucleosomes from parental and newly synthesized histones. We analyzed mutant embryos harboring a deletion of all canonical histone genes, in which nucleosome assembly relies on parental histones from cell cycle 14 onward. Lack of new histone synthesis leads to more accessible chromatin and reduced nucleosome occupancy, since only parental histones are available. This leads to up-regulated and spurious transcription, whereas the control of the developmental transcriptional program is partially maintained. The genomic positions of modified parental histone H2A, H2B, and H3 are largely restored during DNA replication. However, parental histones with active marks become more dispersed within gene bodies, which is linked to transcription. Together, the results suggest that parental histones are recycled to preserve the epigenetic landscape during DNA replication in vivo.
在 DNA 复制过程中，表观遗传的遗传需要从亲代和新合成的组蛋白中协调组装核小体。我们分析了携带所有经典组蛋白基因缺失的突变胚胎，其中核小体组装依赖于细胞周期 14 以后的亲代组蛋白。由于只有亲代组蛋白可用，新的组蛋白合成的缺乏导致染色质更易接近，核小体占有率降低。这导致了上调和虚假转录，而发育转录程序的控制部分得以维持。在 DNA 复制过程中，修饰的亲代组蛋白 H2A、H2B 和 H3 的基因组位置在很大程度上得到了恢复。然而，具有活性标记的亲代组蛋白在基因体内变得更加分散，这与转录有关。总之，这些结果表明，在体内 DNA 复制过程中，亲代组蛋白被回收以维持表观遗传景观。
