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.

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Why screen multiple embryonic-lineage tissues?

To identify systemic interindividual methylation variation.

Source: Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment · DOI · quote verified

What technology enabled the first genomewide human ME screen here?

Bisulfite-seq of PBL and hair follicle methylomes.

Source: Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment · DOI · quote verified

Which infant cohort tested season-of-conception effects?

Gambian infants.

Source: Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment · DOI · quote verified

Where did the two screens converge?

At VTRNA2-1.

Source: Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment · DOI · quote verified

Is VTRNA2-1 variation only blood-specific?

Prior studies lacked concordant multi-tissue variation in the same people; this work shows systemic variation.

Source: Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment · DOI · quote verified

What environmental timing influences VTRNA2-1 methylation?

Periconceptional environment.

Source: Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment · DOI · quote verified

How stable is the epiallele?

Stable over at least 10 years.

Source: Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment · DOI · quote verified

What sequence features associate with metastability?

CGI/SINE depletion and LINE/ERV enrichment over ≥10 kb flanks.

Source: Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment · DOI · quote verified

Why are ERVs noteworthy for MEs?

Documented mouse MEs are linked to IAP (murine ERV) retrotransposition.

Source: Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment · DOI · quote verified

What do transposable elements likely contribute?

Regional methylation patterns that enable stochastic epigenetic variation.

Source: Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment · DOI · quote verified

What caveat do authors note about the ME screen?

It has limitations despite being genomically unbiased.

Source: Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment · DOI · quote verified