Preprint shows transcription across the PWS-SRO is sufficient to trigger de novo DNA methylation at an imprinting centre
Using a human iPSC model, researchers demonstrate that transcription initiated at the AS-SRO drives methylation of the PWS-SRO, illuminating how the Prader-Willi and Angelman syndrome imprinting centre is established.
A new bioRxiv preprint from researchers using a human induced pluripotent stem cell (iPSC) system reports that transcription itself — rather than sequence identity alone — is sufficient to trigger de novo DNA methylation at the imprinting control region linked to Prader-Willi syndrome (PWS) and Angelman syndrome (AS).
The PWS/AS locus on chromosome 15q contains a bipartite imprinting centre: the PWS-SRO, which in normal development acquires maternal-specific methylation, and the AS-SRO, an upstream promoter that drives transcription in oocytes. By engineering the endogenous AS-SRO in human iPSCs to initiate transcription across the PWS-SRO, the authors show that this transcriptional read-through is sufficient to recruit the de novo methylation machinery and establish allele-specific methylation at the PWS-SRO.
The findings advance understanding of how parent-of-origin-specific gene expression is established during development. Both PWS and AS are neurodevelopmental conditions caused by loss of function at this locus, but arise depending on which parental allele is affected — making the imprinting mechanism central to understanding their molecular aetiology. The study is a preprint and has not yet been peer-reviewed. It will be of particular interest to researchers working on genomic imprinting, epigenetic inheritance, and the molecular basis of imprinting disorders.
Plain-language version
For patients, families, and general readers. Educational only — not medical advice.
Prader-Willi syndrome and Angelman syndrome are rare genetic conditions caused by problems with a specific region of chromosome 15. What makes this region unusual is that it behaves differently depending on whether it is inherited from a person's mother or their father — a biological phenomenon called genomic imprinting.
Researchers have now used stem cells grown in the laboratory to investigate exactly how this imprinting is set up. They found that a molecular process called transcription — where a stretch of DNA is read to produce an RNA molecule — is enough to switch on a chemical tag called DNA methylation at the key control region. This tag is what tells the cell which parental copy of the chromosome is which.
This is early laboratory research and does not directly change how either condition is diagnosed or managed. The work is a preprint and has not yet been independently reviewed.
This is an educational summary, not medical advice. If anything here raises questions for you, please speak with your GP or a clinical professional.
Sources
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Primary sourcePreprint bioRxiv (Cold Spring Harbor Laboratory) · 2026-09-14Transcription-driven establishment of DNA methylation at the PWS/AS imprinted region