Open AccessSingle-gene imaging links genome topology, promoter–enhancer communication and transcription control
Author(s) -
Jieru Li,
Angela Hsu,
Yujing Hua,
Guanshi Wang,
Lan Cheng,
Hiroshi Ochiai,
Takashi Yamamoto,
Alexandros Pertsinidis
Publication year - 2020
Publication title -
nature structural and molecular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.448
H-Index - 270
eISSN - 1545-9993
pISSN - 1545-9985
DOI - 10.1038/s41594-020-0493-6
Subject(s) - enhancer , biology , chromatin , gene , transcription factor , promoter , genetics , transcription (linguistics) , chromosome conformation capture , locus (genetics) , regulation of gene expression , locus control region , genome , computational biology , gene expression , linguistics , philosophy
Transcription activation by distal enhancers is essential for cell-fate specification and maintenance of cellular identities. How long-range gene regulation is physically achieved, especially within complex regulatory landscapes of non-binary enhancer-promoter configurations, remains elusive. Recent nanoscopy advances have quantitatively linked promoter kinetics and ~100- to 200-nm-sized clusters of enhancer-associated regulatory factors (RFs) at important developmental genes. Here, we further dissect mechanisms of RF clustering and transcription activation in mouse embryonic stem cells. RF recruitment into clusters involves specific molecular recognition of cognate DNA and chromatin-binding sites, suggesting underlying cis-element clustering. Strikingly, imaging of tagged genomic loci, with ≤1 kilobase and ~20-nanometer precision, in live cells, reveals distal enhancer clusters over the extended locus in frequent close proximity to target genes-within RF-clustering distances. These high-interaction-frequency enhancer-cluster 'superclusters' create nano-environments wherein clustered RFs activate target genes, providing a structural framework for relating genome organization, focal RF accumulation and transcription activation.