Targeted DNA methylation editing in vivo
Kalomoiri, M.; Sorini, C.; Vos, S. V. T.; Camargo, A.; Prakash, C. R.; Svenningsson, P.; Pahlevan Kakhki, M.; Kular, L.; Jagodic, M.
Show abstract
The number of epigenome-wide association studies linking CpG DNA methylation with disease, traits and exposures, continues to rise. Establishing the causation of these associations, despite the rapid development of epigenome editing tools, remains challenging, particularly in vivo. In this study, we developed and characterized three Cre-dependent CRISPR-based mouse lines that enable locus-specific DNA methylation deposition by either constitutive or inducible dCas9-DNMT3A expression. We demonstrate robust locus-specific DNA methylation deposition of MHC class II (H2-Ab1) and interleukin 6 (Il6) genes in bone marrow-derived myeloid cells ex vivo. Moreover, neuron-specific targeting results in decreased cannabinoid receptor 1 (Cnr1) expression in striatal neurons in vivo. Notably, we demonstrate that the causal effect of DNA methylation on gene expression is locus-dependent, reinforcing the necessity of such editing tools for detailed understanding of the role of DNA methylation and for addressing the causality of disease-associated CpGs.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- CRISPR/Cas9-Mediated Excision of ALS/FTD-Causing Hexanucleotide Repeat Expansion in C9ORF72 rescues major disease mechanisms in vivo and in vitro 97%
- A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD 97%
- CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment 96%
Similar papers in this journal
- Parallel functional testing identifies enhancers active in early postnatal mouse brain 96%
- Whole brain delivery of an instability-prone Mecp2 transgene improves behavioral and molecular pathological defects in mouse models of Rett syndrome 96%
- Rapid and specific degradation of endogenous proteins in mouse models using auxin-inducible degrons 96%
Similar papers in this journal
- Neurons burdened by DNA double strand breaks incite microglia activation through antiviral-like signaling in neurodegeneration. 96%
- L1 retrotransposons drive human neuronal transcriptome complexity and functional diversification 95%
- Growth hormone is required for hippocampal engram cell maturation 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.