Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna Biocenter (VBC), Vienna, Austria.
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Nat Cell Biol. 2021 Apr;23(4):391-400. doi: 10.1038/s41556-021-00658-1. Epub 2021 Apr 8.
Mobile transposable elements (TEs) not only participate in genome evolution but also threaten genome integrity. In healthy cells, TEs that encode all of the components that are necessary for their mobility are specifically silenced, yet the precise mechanism remains unknown. Here, we characterize the mechanism used by a conserved class of chromatin remodelers that prevent TE mobility. In the Arabidopsis chromatin remodeler DECREASE IN DNA METHYLATION 1 (DDM1), we identify two conserved binding domains for the histone variant H2A.W, which marks plant heterochromatin. DDM1 is necessary and sufficient for the deposition of H2A.W onto potentially mobile TEs, yet does not act on TE fragments or host protein-coding genes. DDM1-mediated H2A.W deposition changes the properties of chromatin, resulting in the silencing of TEs and, therefore, prevents their mobility. This distinct mechanism provides insights into the interplay between TEs and their host in the contexts of evolution and disease, and potentiates innovative strategies for targeted gene silencing.
移动转座元件 (TEs) 不仅参与基因组进化，还威胁基因组完整性。在健康细胞中，编码其移动所需的所有成分的 TEs 被特异性沉默，但确切的机制仍不清楚。在这里，我们描述了一类保守的染色质重塑因子用于防止 TEs 移动的机制。在拟南芥染色质重塑因子 DECREASE IN DNA METHYLATION 1 (DDM1) 中，我们鉴定出两个组蛋白变体 H2A.W 的保守结合域，H2A.W 标记植物异染色质。DDM1 对于潜在可移动 TEs 上 H2A.W 的沉积是必需和充分的，但不作用于 TE 片段或宿主蛋白编码基因。DDM1 介导的 H2A.W 沉积改变染色质的性质，导致 TEs 的沉默，从而阻止它们的移动。这种独特的机制提供了关于 TEs 与其宿主在进化和疾病背景下相互作用的深入了解，并为靶向基因沉默提供了创新策略。
