VTRNA2-1: an environment-sensitive human epiallele
Independent genome-wide methylation screens converge on VTRNA2-1 as a systemic metastable epiallele shaped by periconceptional environment and stable for years.
Source
Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment
Study at a glance
- Design
- Other — Multi-tissue metastable-epiallele screens plus Gambian season-of-conception methylation analyses
- N
- N=215 · Season-of-conception contrast: 110 dry-season vs 105 rainy-season conceptions; additional multi-tissue discovery screens
- Population
- Human multi-tissue DNA methylomes and Gambian infant cohorts
- Outcome
- Systemic interindividual methylation at VTRNA2-1 and periconceptional environment effects
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What they did
Authors screened multi-tissue DNA methylomes for systemic interindividual variation, then tested season-of-conception effects in Gambian infants, converging on VTRNA2-1.
What they found
VTRNA2-1 shows concordant multi-tissue methylation differences, is partly set by periconceptional environment, and remains stable ≥10 years; ME regions are depleted for CGIs/SINEs and enriched for LINEs/ERVs.
The limits
What it doesn't show
Epiallele status is not itself proof of disease causation in every tissue; screens have genomic biases despite being genomewide.
Key terms
- Metastable epiallele (ME)
- Locus with systemic, stochastic methylation differences established early and mitotically stable.
- VTRNA2-1
- Vault RNA / putative tumor-suppressor locus highlighted as a human ME.
- Periconceptional environment
- Nutritional/environmental conditions around conception.
- Bisulfite-seq
- Sequencing method measuring CpG methylation after bisulfite conversion.
- ERV/LINE enrichment
- Retrotransposon classes enriched near metastable regions.
Flashcards
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Quiz yourself
Convergent locus:
Common questions
Why screen multiple tissues?
To find systemic (not tissue-specific) methylation variation.
Which locus converged?
VTRNA2-1.
How durable is the methylation state?
Stable over at least 10 years.
What genomic features mark MEs?
CGI/SINE depletion; LINE/ERV enrichment.
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