Direct interrogation of the role of H3K9 in metazoan heterochromatin function
Open accessAbstract
A defining feature of heterochromatin is methylation of Lys9 of histone H3 (H3K9me), a binding site for heterochromatin protein 1 (HP1). Although H3K9 methyltransferases and HP1 are necessary for proper heterochromatin structure, the specific contribution of H3K9 to heterochromatin function and animal development is unknown. Using our recently developed platform to engineer histone genes in Drosophila, we generated H3K9R mutant flies, separating the functions of H3K9 and nonhistone substrates of H3K9 methyltransferases. Nucleosome occupancy and HP1a binding at pericentromeric heterochromatin are markedly decreased in H3K9R mutants. Despite these changes in chromosome architecture, a small percentage of H3K9R mutants complete development. Consistent with this result, expression of most protein-coding genes, including those within heterochromatin, is similar between H3K9R and controls. In contrast, H3K9R mutants exhibit increased open chromatin and transcription from piRNA clusters and transposons, resulting in transposon mobilization. Hence, transposon silencing is a major developmental function of H3K9.
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The histone replacement system abolishes all modifications of H3K9 and mainly manifests itself in derepression of TEs likely due to the loss of H3K9me2/3 marks.
“Although this replacement abolishes all modifications of H3K9, it mainly manifests itself in derepression of TEs likely due to the loss of H3K9me2/3 marks (71).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [71]
The Abstract and Results report that H3K9R replacement leaves most protein-coding expression relatively normal while derepressing most transposon families; the Results link transposon activation to loss of HP1a and a repressive chromatin environment. The claim that it abolishes all H3K9 modifications is too broad: the Results report unchanged H3K9me3 signal on chromosome arms, potentially from replication-independent H3.3. Our copy provides no page numbers for these passages. (LLM, conf=0.87)
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Writing, erasing and reading histone lysine methylations
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“Although this replacement abolishes all modifications of H3K9, it mainly manifests itself in derepression of TEs likely due to the loss of H3K9me2/3 marks (71).”
BackgroundMethodInfluential
- Authors
- Penke, T. J. R., McKay, D. J., Strahl, B. D., Matera, A. G., & Duronio, R. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2016-08-15
- Volume
- 30
- Issue
- 16
- Pages
- 1866-1880
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC5024684
- OpenAlex
- W2509429928
- Cited by
- 74
- References
- 11
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 10 · 2023: 9 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 9 · 2018: 13 · 2017: 9
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Genes & Development (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institute on Drug Abuse (R01DA036897)
- National Institute of General Medical Sciences (T32GM007092, F31GM115194)
- 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 › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- H3K9 methylation, heterochromatin, HP1α, pericentromeric heterochromatin, transposon silencing, piRNA clusters, transposon mobility, open chromatin, nucleosome occupancy, histone methyltransferase, Drosophila, animal development
- MeSH terms
- Chromobox Protein Homolog 5, Animals, Chromosomal Proteins, Non-Histone, Chromosomes, DNA Transposable Elements, Drosophila melanogaster, Heterochromatin, Histones, Mutation, Nucleosomes, Protein Binding, Histone-Lysine N-Methyltransferase, Gene Expression Regulation, Developmental, Gene Silencing, Drosophila Proteins, RNA, Small Interfering
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