ArticleGenes & development2003
Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation.
Article in Genes & development, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers.
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178 citing papers in PubMed.
- Extensive binding of poorly characterized human transcription factors to genomic dark matter.Nature communications · 2026Article
- Single-cell chromatin state transitions during epigenetic memory formation.Science advances · 2026Article
- HP1β and H3K9me3 Regulate Olfactory Receptor Choice and Transcriptional Identity.International journal of molecular sciences · 2026Article
- Engineering Inducible Cell Fate Transitions by Harnessing Epigenetic Silencing.bioRxiv : the preprint server for biology · 2025Article
- Article
- HP1β and H3K9me3 Regulate Olfactory Receptor Choice and Transcriptional Identity.bioRxiv : the preprint server for biology · 2025Article
- Differential Crosslinking and Contractile Motors Drive Nuclear Chromatin Compaction.bioRxiv : the preprint server for biology · 2025Article
- Article
- HP1-Mediated Silencing of theJournal of developmental biology · 2025Article
- Prognosis, immunological features and potential mechanisms of HKR1 in prostate cancer via single-cell and bulk RNA-sequencing.BMC cancer · 2025Article
- SUMOylation of TRIM28 is positively modulated by the BTB/POZ domain of Kaiso.Molecular biology reports · 2025Article
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- ChAHP2 and ChAHP control diverse retrotransposons by complementary activities.Genes & development · 2024Article
- SETDB1 deletion causes DNA demethylation and upregulation of multiple zinc-finger genes.Molecular biology reports · 2024Article
- Interplay between charge distribution and DNA in shaping HP1 paralog phase separation and localization.eLife · 2024Article
- Investigation of Glycosylphosphatidylinositol (GPI)-Plasma Membrane Interaction in Live Cells and the Influence of GPI Glycan Structure on the Interaction.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- Fluorescent Reporter Systems to Investigate Chromatin Effector Proteins in Living Cells.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Temporal Profiling of Host Proteome against DifferentMicroorganisms · 2023Article
- The functions of SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) in biological process and disease.Epigenetics & chromatin · 2023Review
- Unraveling the role of ZNF506 as a human PBS-pro-targeting protein for ERVP repression.Nucleic acids research · 2023Article
118 more citing papers are in PubMed but not listed here.
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9 authors.
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Abstract
Heterochromatin protein 1 (HP1) is a key component of constitutive heterochromatin in Drosophila and is required for stable epigenetic gene silencing classically observed as position effect variegation. Less is known of the family of mammalian HP1 proteins, which may be euchromatic, targeted to expressed loci by repressor-corepressor complexes, and retained there by Lys 9-methylated histone H3 (H3-MeK9). To characterize the physical properties of euchromatic loci bound by HP1, we developed a strategy for regulated recruitment of HP1 to an expressed transgene in mammalian cells by using a synthetic, hormone-regulated KRAB repression domain. We show that its obligate corepressor, KAP1, can coordinate all the machinery required for stable gene silencing. In the presence of hormone, the transgene is rapidly silenced, spatially recruited to HP1-rich nuclear regions, assumes a compact chromatin structure, and is physically associated with KAP1, HP1, and the H3 Lys 9-specific methyltransferase, SETDB1, over a highly localized region centered around the promoter. Remarkably, silencing established by a short pulse of hormone is stably maintained for >50 population doublings in the absence of hormone in clonal-cell populations, and the silent transgenes in these clones show promoter hypermethylation. Thus, like variegation in Drosophila, recruitment of mammalian HP1 to a euchromatic promoter can establish a silenced state that is epigenetically heritable.
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