丹麦哥本哈根大学Anja Groth小组发现,被修饰过的H2A-H2B的回收提供染色质状态的短期记忆。该项研究成果于2023年2月6日在线发表在《细胞》杂志上。
通过定量基因组学,研究人员测量了DNA复制和整个细胞周期H2A-H2B的修饰和H2A.Z。研究人员发现H2AK119ub1、H2BK120ub1和H2A.Z在DNA复制过程中被精确回收。修饰后的H2A-H2B通过滞后链上的POLA1对称分离到子链上,但与H3-H4回收无关。复制后,H2A-H2B修饰和变体景观被快速恢复,H2AK119ub1指导H3K27me3的精确恢复。这项工作揭示了DNA复制过程中亲本H2A-H2B的表观遗传传递,并确定了H3-H4和H2A-H2B修饰在表观基因组传递中的交流。研究人员提出,回收的H2A-H2B修饰的快速短期记忆有助于恢复稳定的H3-H4染色质状态。
据悉,染色质景观在DNA复制过程中被破坏,但又必须被忠实地恢复,以维持基因组调控和细胞身份。组蛋白H3-H4修饰景观通过亲本组蛋白回收和新组蛋白修饰得以恢复。DNA复制如何影响组蛋白H2A-H2B目前尚不清楚。
附:英文原文
Title: Recycling of modified H2A-H2B provides short-term memory of chromatin states
Author: Valentin Flury, Nazaret Reverón-Gómez, Nicolas Alcaraz, Kathleen R. Stewart-Morgan, Alice Wenger, Robert J. Klose, Anja Groth
Issue&Volume: 2023-02-06
Abstract: Chromatin landscapes are disrupted during DNA replication and must be restored faithfully to maintain genome regulation and cell identity. The histone H3-H4 modification landscape is restored by parental histone recycling and modification of new histones. How DNA replication impacts on histone H2A-H2B is currently unknown. Here, we measure H2A-H2B modifications and H2A.Z during DNA replication and across the cell cycle using quantitative genomics. We show that H2AK119ub1, H2BK120ub1, and H2A.Z are recycled accurately during DNA replication. Modified H2A-H2B are segregated symmetrically to daughter strands via POLA1 on the lagging strand, but independent of H3-H4 recycling. Post-replication, H2A-H2B modification and variant landscapes are quickly restored, and H2AK119ub1 guides accurate restoration of H3K27me3. This work reveals epigenetic transmission of parental H2A-H2B during DNA replication and identifies cross talk between H3-H4 and H2A-H2B modifications in epigenome propagation. We propose that rapid short-term memory of recycled H2A-H2B modifications facilitates restoration of stable H3-H4 chromatin states.
DOI: 10.1016/j.cell.2023.01.007
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00007-7