ArticleEpigenetics & chromatin2014
Targeted gene suppression by inducing de novo DNA methylation in the gene promoter.
Article in Epigenetics & chromatin, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Human cytomegalovirus hijacks host stress response fueling replication stress and genome instability.Cell death and differentiation · 2022Article
- Pluripotency exit is guided by the Peln1-mediated disruption of intrachromosomal architecture.The Journal of cell biology · 2022Article
- KRAB-Induced Heterochromatin Effectively SilencesInternational journal of molecular sciences · 2020Article
- Oplr16 serves as a novel chromatin factor to control stem cell fate by modulating pluripotency-specific chromosomal looping and TET2-mediated DNA demethylation.Nucleic acids research · 2020Article
- DNA hypermethylation of the promoter attenuates forkhead box protein 3 (FOXP3) expression in hepatocellular carcinoma cells.Translational cancer research · 2019Article
- The expression signature of cancer-associated KRAB-ZNF factors identified in TCGA pan-cancer transcriptomic data.Molecular oncology · 2019Article
- Epigenetic Targeting of Granulin in Hepatoma Cells by Synthetic CRISPR dCas9 Epi-suppressors.Molecular therapy. Nucleic acids · 2018Article
- TRIM28 and Interacting KRAB-ZNFs Control Self-Renewal of Human Pluripotent Stem Cells through Epigenetic Repression of Pro-differentiation Genes.Stem cell reports · 2017Article
- Molecular structures guide the engineering of chromatin.Nucleic acids research · 2017Article
- Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells.Stem cells international · 2017Article
- Antitumor potential of a synthetic interferon-alpha/PLGF-2 positive charge peptide hybrid molecule in pancreatic cancer cells.Scientific reports · 2015Article
- Strategies for precision modulation of gene expression by epigenome editing: an overview.Epigenetics & chromatin · 2015Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTargeted gene silencing is an important approach in both drug development and basic research. However, the selection of a potent suppressor has become a significant hurdle to implementing maximal gene inhibition for this approach. We attempted to construct a 'super suppressor' by combining the activities of two suppressors that function through distinct epigenetic mechanisms.
resultsGene targeting vectors were constructed by fusing a GAL4 DNA-binding domain with a epigenetic suppressor, including CpG DNA methylase Sss1, histone H3 lysine 27 methylase vSET domain, and Kruppel-associated suppression box (KRAB). We found that both Sss1 and KRAB suppressors significantly inhibited the expression of luciferase and copGFP reporter genes. However, the histone H3 lysine 27 methylase vSET did not show significant suppression in this system. Constructs containing both Sss1 and KRAB showed better inhibition than either one alone. In addition, we show that KRAB suppressed gene expression by altering the histone code, but not DNA methylation in the gene promoter. Sss1, on the other hand, not only induced de novo DNA methylation and recruited Heterochromatin Protein 1 (HP1a), but also increased H3K27 and H3K9 methylation in the promoter.
conclusionsEpigenetic studies can provide useful data for the selection of suppressors in constructing therapeutic vectors for targeted gene silencing.
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