Single-gene imaging links genome topology, promoter–enhancer communication and transcription control Journal Article

   


Authors: Li, J.; Hsu, A.; Hua, Y.; Wang, G.; Cheng, L.; Ochiai, H.; Yamamoto, T.; Pertsinidis, A.
Article Title: Single-gene imaging links genome topology, promoter–enhancer communication and transcription control
Abstract: 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. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Keywords: controlled study; promoter region; transcription initiation; gene frequency; genome analysis; chromatin; molecular recognition; binding site; enhancer region; article; mouse embryonic stem cell
Journal Title: Nature Structural and Molecular Biology
Volume: 27
Issue: 11
ISSN: 1545-9993
Publisher: Nature Publishing Group  
Date Published: 2020-11-01
Start Page: 1032
End Page: 1040
Language: English
DOI: 10.1038/s41594-020-0493-6
PUBMED: 32958948
PROVIDER: scopus
PMCID: PMC7644657
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091139910&doi=10.1038%2fs41594-020-0493-6&partnerID=40&md5=8f4730caa245fe7930e1860ba026c25c
Notes: Article -- Export Date: 1 December 2020 -- Source: Scopus
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MSK Authors
  1. Alexandros Pertsinidis
    16 Pertsinidis
  2. Guanshi Wang
    6 Wang
  3. Jieru Li
    6 Li
  4. Angela Hsu
    1 Hsu
  5. Yujing Hua
    1 Hua
  6. Lingling Cheng
    1 Cheng
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