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Updated: Feb 2, 2026
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Localized RNAi and Ectopic Gene Expression in the Medicinal Leech
Published on: April 17, 2008
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Targets and genomic constraints of ectopic Dnmt3b expression
Yingying Zhang1, Jocelyn Charlton1,2, Rahul Karnik1
1Department of Stem Cell and Regenerative Biology, Harvard University, Massachusetts, United States.
Elife
|November 24, 2018
Summary
Deregulation of DNA methyltransferase DNMT3B in cancer can lead to abnormal DNA methylation. This study reveals transcriptional state and chromatin landscape predict aberrant DNMT3B targeting in mammalian genomes.
Area of Science:
- Genomics
- Epigenetics
- Cancer Biology
Background:
- DNA methylation is crucial for mammalian genomes, with its enzymes tightly regulated.
- DNMT3B (DNA methyltransferase 3B) deregulation is common in cancers, but its ectopic genomic targets remain poorly understood.
Purpose of the Study:
- To define the rules governing abnormal DNMT3B targeting in a mouse model.
- To investigate the cellular constraints on DNMT3B activity.
- To understand the basis for CpG island hypermethylation in cancer.
Main Methods:
- Utilized an inducible transgenic mouse model to study DNMT3B activity.
- Performed genome-wide analyses and ultra-deep locus-specific bisulfite sequencing.
- Assessed the relationship between DNA methylation, H3K27me3, and chromatin landscape.
Main Results:
- Identified transcriptional state and chromatin landscape as key predictors of aberrant DNMT3B targeting.
- Observed transient co-occurrence of H3K27me3 with DNMT3B-induced DNA methylation at CpG islands.
- Demonstrated distributive activity of ectopically expressed Dnmt3b leading to discordant CpG island hypermethylation.
Conclusions:
- Provides a framework for understanding aberrant DNA methylation in cancer.
- Offers new insights into the interpretation of cancer methylomes.
- Highlights the importance of chromatin context in directing DNA methylation patterns.
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