意大利欧洲分子生物学实验室Jamie A. Hackett研究组发现，系统性表观基因组编辑可捕获染色质修饰的背景依赖性指导功能。这一研究成果于2024年5月9日在线发表在国际学术期刊《自然—遗传学》上。

据了解，染色质修饰与基因表达模式的调控有关，但它们对转录的因果作用和背景依赖性影响仍未解决。

附：英文原文

Title: Systematic epigenome editing captures the context-dependent instructive function of chromatin modifications

Author: Policarpi, Cristina, Munaf, Marzia, Tsagkris, Stylianos, Carlini, Valentina, Hackett, Jamie A.

Issue&Volume: 2024-05-09

Abstract: Chromatin modifications are linked with regulating patterns of gene expression, but their causal role and context-dependent impact on transcription remains unresolved. Here we develop a modular epigenome editing platform that programs nine key chromatin modifications, or combinations thereof, to precise loci in living cells. We couple this with single-cell readouts to systematically quantitate the magnitude and heterogeneity of transcriptional responses elicited by each specific chromatin modification. Among these, we show that installing histone H3 lysine 4 trimethylation (H3K4me3) at promoters can causally instruct transcription by hierarchically remodeling the chromatin landscape. We further dissect how DNA sequence motifs influence the transcriptional impact of chromatin marks, identifying switch-like and attenuative effects within distinct cis contexts. Finally, we examine the interplay of combinatorial modifications, revealing that co-targeted H3K27 trimethylation (H3K27me3) and H2AK119 monoubiquitination (H2AK119ub) maximizes silencing penetrance across single cells. Our precision-perturbation strategy unveils the causal principles of how chromatin modification(s) influence transcription and dissects how quantitative responses are calibrated by contextual interactions.

DOI: 10.1038/s41588-024-01706-w

Source: https://www.nature.com/articles/s41588-024-01706-w