法国索邦大学Raphaël Margueron、丹麦哥本哈根大学Cecilia Lövkvist等研究人员合作发现，一个顺式作用机制介导哺乳动物中Polycomb靶基因的转录记忆。相关论文于2021年11月15日在线发表在《自然—遗传学》杂志上。

利用全局性的染色质扰动和局部的、时间控制的转录调控，研究人员证实了基因转录激活的表观遗传记忆。这一特性在细胞分化过程中出现，并允许基因在短暂的转录刺激后被稳定地切换。这种在Polycomb靶点的转录记忆状态是顺式作用的；然而，这种记忆不是仅仅依靠组蛋白修饰的读写传播，而是也与对立Polycomb蛋白的激活输入的强度有关，因此随着细胞环境而变化。研究人员的数据和计算模拟表明了一个模型，即转录记忆产生于Polycomb介导的沉默和活跃的转录之间的双负反馈。因此，Polycomb靶标的转录记忆不仅取决于组蛋白修饰，还取决于基因调控网络和细胞的基本特性。

据介绍，基因表达状态的表观遗传使单一基因组能够保持不同的细胞特性。组蛋白修饰如何对这一过程作出贡献仍不清楚。

附：英文原文

Title: A cis-acting mechanism mediates transcriptional memory at Polycomb target genes in mammals

Author: Holoch, Daniel, Wassef, Michel, Lvkvist, Cecilia, Zielinski, Dina, Aflaki, Setareh, Lombard, Brangre, Hry, Tiphaine, Loew, Damarys, Howard, Martin, Margueron, Raphal

Issue&Volume: 2021-11-15

Abstract: Epigenetic inheritance of gene expression states enables a single genome to maintain distinct cellular identities. How histone modifications contribute to this process remains unclear. Using global chromatin perturbations and local, time-controlled modulation of transcription, we establish the existence of epigenetic memory of transcriptional activation for genes that can be silenced by the Polycomb group. This property emerges during cell differentiation and allows genes to be stably switched after a transient transcriptional stimulus. This transcriptional memory state at Polycomb targets operates in cis; however, rather than relying solely on read-and-write propagation of histone modifications, the memory is also linked to the strength of activating inputs opposing Polycomb proteins, and therefore varies with the cellular context. Our data and computational simulations suggest a model whereby transcriptional memory arises from double-negative feedback between Polycomb-mediated silencing and active transcription. Transcriptional memory at Polycomb targets thus depends not only on histone modifications but also on the gene-regulatory network and underlying identity of a cell.

DOI: 10.1038/s41588-021-00964-2

Source: https://www.nature.com/articles/s41588-021-00964-2