In vivo HP1 targeting causes large-scale chromatin condensation and enhanced histone lysine methylation
Open accessAbstract
Changes in chromatin structure are a key aspect in the epigenetic regulation of gene expression. We have used a lac operator array system to visualize by light microscopy the effect of heterochromatin protein 1 (HP1) alpha (HP1alpha) and HP1beta on large-scale chromatin structure in living mammalian cells. The structure of HP1, containing a chromodomain, a chromoshadow domain, and a hinge domain, allows it to bind to a variety of proteins. In vivo targeting of an enhanced green fluorescent protein-tagged HP1-lac repressor fusion to a lac operator-containing, gene-amplified chromosome region causes local condensation of the higher-order chromatin structure, recruitment of the histone methyltransferase SETDB1, and enhanced trimethylation of histone H3 lysine 9. Polycomb group proteins of both the HPC/HPH and the EED/EZH2 complexes, which are involved in the heritable repression of gene activity, are not recruited to the amplified chromosome region by HP1alpha and HP1beta in vivo targeting. HP1alpha targeting causes the recruitment of endogenous HP1beta to the chromatin region and vice versa, indicating a direct interaction between the two HP1 homologous proteins. Our findings indicate that HP1alpha and HP1beta targeting is sufficient to induce heterochromatin formation.
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HP1 tethering to lacO induces chromatin compaction and silencing.
“HP1 tethering to lacO has been previously shown to induce chromatin compaction and silencing”
From Activation of DNA Damage Response Signaling by Condensed Chromatin (2014) · cites this paper as Verschure et al., 2005
Tethering HP1α, HP1β, HP1γ, or SUV3-9 to lacO arrays induces local chromatin compaction and H3K9me3 enrichment, with reduced nuclease accessibility.
“tethering of these repressive chromatin proteins led to more compact arrays”
From Activation of DNA Damage Response Signaling by Condensed Chromatin (2014) · cites this paper as Verschure et al., 2005
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- Authors
- Verschure, P. J., van der Kraan, I., de Leeuw, W., van der Vlag, J., Carpenter, A. E., Belmont, A. S., & van Driel, R.
- Affiliations
- University of Amsterdam (NL)
- Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam
- Center for Mathematics and Computer Science, CWI
- Nephrology Research Lab, Nijmegen Center for Molecular Life Sciences, Division of Nephrology, University Medical Center
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Verschure, Pernette J.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2005-06-01
- Volume
- 25
- Issue
- 11
- Pages
- 4552-4564
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1140641
- OpenAlex
- W2154071588
- Cited by
- 183
- References
- 56
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 11 · 2020: 10 · 2019: 9 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 7 · 2014: 10 · 2013: 8 · 2012: 14
- FWCI
- 6.02
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Centrum Wiskunde & Informatica (CWI), the national research institute for mathematics and computer science in the Netherlands (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- National Institute of General Medical Sciences (R01GM042516)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- HP1, HP1α, HP1β, chromatin condensation, histone H3 lysine 9 trimethylation, SETDB1, Polycomb group proteins, heterochromatin formation, epigenetic silencing, chromatin structure
- MeSH terms
- Chromobox Protein Homolog 5, Cells, Cultured, Chromosomal Proteins, Non-Histone, Chromosomes, Human, Heterochromatin, Histones, Humans, Lysine, Methylation, Operator Regions, Genetic, Histone-Lysine N-Methyltransferase, Protein Methyltransferases, Recombinant Fusion Proteins, Repressor Proteins, Gene Silencing, Green Fluorescent Proteins
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