Cited by 70Genomics and Chromatin DynamicsNuclear Structure and FunctionChromosomal and Genetic Variations

Poly(ADP-ribosyl)ation regulates insulator function and intrachromosomal interactions in Drosophila

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Ong, Chin-Tong, Van Bortle, Kevin, Ramos, Edward, Corces, Victor G.·2013·Cell

Abstract

Insulators mediate inter- and intrachromosomal contacts to regulate enhancer-promoter interactions and establish chromosome domains. The mechanisms by which insulator activity can be regulated to orchestrate changes in the function and three-dimensional arrangement of the genome remain elusive. Here, we demonstrate that Drosophila insulator proteins are poly(ADP-ribosyl)ated and that mutation of the poly(ADP-ribose) polymerase (Parp) gene impairs their function. This modification is not essential for DNA occupancy of insulator DNA-binding proteins dCTCF and Su(Hw). However, poly(ADP-ribosyl)ation of K566 in CP190 promotes protein-protein interactions with other insulator proteins, association with the nuclear lamina, and insulator activity in vivo. Consistent with these findings, the nuclear clustering of CP190 complexes is disrupted in Parp mutant cells. Importantly, poly(ADP-ribosyl)ation facilitates intrachromosomal interactions between insulator sites measured by 4C. These data suggest that the role of insulators in organizing the three-dimensional architecture of the genome may be modulated by poly(ADP-ribosyl)ation.

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Authors
Ong, C.-T., Van Bortle, K., Ramos, E., & Corces, V. G.
Affiliations
Emory University (US)
Corresponding author
Corces, Victor G.
Venue
Cell
Publisher
Elsevier BV
Published
2013-09
Volume
155
Issue
1
Pages
148-159
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2080915753
Cited by
70
References
59
Citations by year
2026: 2 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 12 · 2015: 5 · 2014: 10 · 2013: 4
FWCI
4.63
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • U.S. Public Health Service
  • National Institute of General Medical Sciences (R01GM035463)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
poly(ADP-ribosyl)ation, insulators, CP190, poly(ADP-ribose) polymerase, Su(Hw), 3D genome organization, nuclear lamina, protein-protein interaction, Drosophila, chromatin structure
MeSH terms
Animals, Cell Differentiation, DNA-Binding Proteins, Drosophila melanogaster, Mutation, Poly Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Nuclear Matrix, Drosophila Proteins, Insulator Elements, Chromosomes, Insect, Polytene Chromosomes

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