ArticleProceedings of the National Academy of Sciences of the United States of America2015
Histone chaperone CAF-1 mediates repressive histone modifications to protect preimplantation mouse embryos from endogenous retrotransposons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 75 citations in OpenAlex.
- Newly synthesized histones: passive or active players in the regulation of epigenetic inheritance?Nucleic acids research · 2026Review
- Chromatin Assembly Factor 1 is required for normal structure and function of facultative heterochromatin inbioRxiv : the preprint server for biology · 2026Article
- Hat1 Orchestrates Heterochromatin Inheritance by Regulating Localization of H3K9 Methyltransferases.bioRxiv : the preprint server for biology · 2026Article
- A de novo H3.2K9me2 deposition pathway establishes heterochromatin for suppressing transposon mobilization during fly somatic development.Nucleic acids research · 2026Article
- Epigenome dynamics in early mammalian embryogenesis.Nature reviews. Genetics · 2025Review
- Expression of LINE-1 elements is required for preimplantation development and totipotency.Genes & diseases · 2025Review
- Pwp1 inhibition impairs the development and early lineage commitment of mouse preimplantation embryos.The Journal of reproduction and development · 2025Article
- Histone chaperones coupled to DNA replication and transcription control divergent chromatin elements to maintain cell fate.Genes & development · 2025Article
- H3K27 dimethylation dynamics reveal stepwise establishment of facultative heterochromatin in early mouse embryos.Nature cell biology · 2025Article
- Regulation of endogenous retroviruses in murine embryonic stem cells and early embryos.Journal of molecular cell biology · 2024Review
- When Dad's Stress Gets under Kid's Skin-Impacts of Stress on Germline Cargo and Embryonic Development.Biomolecules · 2023Review
- ATM, KAP1 and the Epstein-Barr virus polymerase processivity factor direct traffic at the intersection of transcription and replication.Nucleic acids research · 2023Article
- Histone 4 lysine 20 tri-methylation: a key epigenetic regulator in chromatin structure and disease.Frontiers in genetics · 2023Review
- Transposons Acting as Competitive Endogenous RNAs: In-Silico Evidence from Datasets Characterised by L1 Overexpression.Biomedicines · 2022Article
- Epigenetic Reprogramming in Early Animal Development.Cold Spring Harbor perspectives in biology · 2022Review
- Histone chaperone HIRA complex regulates retrotransposons in embryonic stem cells.Stem cell research & therapy · 2022Article
- Highly rigid H3.1/H3.2-H3K9me3 domains set a barrier for cell fate reprogramming in trophoblast stem cells.Genes & development · 2022Article
- Histones and their chaperones: Adaptive remodelers of an ever-changing chromatinic landscape.Frontiers in genetics · 2022Review
- Histone Chaperones as Cardinal Players in Development.Frontiers in cell and developmental biology · 2022Review
- Suppression of endogenous retroviral enhancers in mouse embryos derived from somatic cell nuclear transfer.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substantial proportions of mammalian genomes comprise repetitive elements including endogenous retrotransposons. Although these play diverse roles during development, their appropriate silencing is critically important in maintaining genomic integrity in the host cells. The major mechanism for retrotransposon silencing is DNA methylation, but the wave of global DNA demethylation that occurs after fertilization renders preimplantation embryos exceptionally hypomethylated. Here, we show that hypomethylated preimplantation mouse embryos are protected from retrotransposons by repressive histone modifications mediated by the histone chaperone chromatin assembly factor 1 (CAF-1). We found that knockdown of CAF-1 with specific siRNA injections resulted in significant up-regulation of the retrotransposons long interspersed nuclear element 1, short interspersed nuclear element B2, and intracisternal A particle at the morula stage. Concomitantly, increased histone H2AX phosphorylation and developmental arrest of the majority (>95%) of embryos were observed. The latter was caused at least in part by derepression of retrotransposons, as treatment with reverse transcriptase inhibitors rescued some embryos. Importantly, ChIP analysis revealed that CAF-1 mediated the replacement of H3.3 with H3.1/3.2 at the retrotransposon regions. This replacement was associated with deposition of repressive histone marks, including trimethylation of histone H3 on lysine 9 (H3K9me3), H3K9me2, H3K27me3, and H4K20me3. Among them, H4K20me3 and H3K9me3 seemed to play predominant roles in retrotransposon silencing, as assessed by knockdown of specific histone methyltransferases and forced expression of unmethylatable mutants of H3.1K9 and H4K20. Our data thus indicate that CAF-1 is an essential guardian of the genome in preimplantation mouse embryos by deposition of repressive histone modifications via histone variant replacement.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.