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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Inspect source passages
VTRNA2-1: an environment-sensitive human epiallele
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
Methylation at this epiallele is stable over at least 10 years.
Further, we demonstrated that this is partially determined by periconceptional environment, and is stable over at least 10 years.
Why screen multiple embryonic-lineage tissues?
screening for concordant variation in multiple tissues representing different embryonic lineages, is unique in enabling the identification of systemic interindividual variation [].
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.
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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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