生物
染色质
DNA甲基化
核小体
遗传学
表观遗传学
DNA
发起人
组蛋白
嘉雅宠物
计算生物学
基因
基因表达
作者
Cyril Esnault,Talha Magat,Amal Zine El Aabidine,Encar García-Oliver,Anne Cucchiarini,Soumya Bouchouika,David Llères,Lutz Goerke,Yu Luo,Daniela Verga,Laurent Lacroix,Robert Feil,Salvatore Spicuglia,Jean‐Louis Mergny,Jean-Christophe Andrau
出处
期刊:Nature Genetics
[Springer Nature]
日期:2023-07-03
卷期号:55 (8): 1359-1369
被引量:10
标识
DOI:10.1038/s41588-023-01437-4
摘要
Metazoan promoters are enriched in secondary DNA structure-forming motifs, such as G-quadruplexes (G4s). Here we describe ‘G4access’, an approach to isolate and sequence G4s associated with open chromatin via nuclease digestion. G4access is antibody- and crosslinking-independent and enriches for computationally predicted G4s (pG4s), most of which are confirmed in vitro. Using G4access in human and mouse cells, we identify cell-type-specific G4 enrichment correlated with nucleosome exclusion and promoter transcription. G4access allows measurement of variations in G4 repertoire usage following G4 ligand treatment, HDAC and G4 helicases inhibitors. Applying G4access to cells from reciprocal hybrid mouse crosses suggests a role for G4s in the control of active imprinting regions. Consistently, we also observed that G4access peaks are unmethylated, while methylation at pG4s correlates with nucleosome repositioning on DNA. Overall, our study provides a new tool for studying G4s in cellular dynamics and highlights their association with open chromatin, transcription and their antagonism to DNA methylation. G4access is a nuclease-based method for identifying DNA G-quadruplex forming regions genome-wide in open chromatin using sequencing. Application across a range of cell types and species highlights associations of G-quadruplexes with various epigenetic and regulatory features.
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