Dan Sarni

Dan Sarni

@dansarni.bsky.social

Postdoc in the Jackson lab @mrc_hgu. Genome instability, DNA methylation and replication

25 followers 29 following12 posts

Dan Sarni reposted

@sproullab.bsky.social

Last week to apply for this. If you are interested in working on cool project to understand the role of DNA methylation in regulating transcription please apply!

Duncan Sproul@sproullab.bsky.social

🚨 #Postdoc position open. Want to understand non-canonical #epigenetic regulation of mammalian transcription? Come work @uoe-igc.bsky.social in Edinburgh! We’re looking for a motivated & collaborative colleague with a strong track record. 📅 14 October 2026 📢 Please share Apply here 👇

elxw.fa.em3.oraclecloud.comPost-Doctoral Research AssociateAn exciting postdoctoral position is available to research the role of epigenetic marks in gene regulation.

Dan Sarni reposted

Institute of Genetics and Cancer

@uoe-igc.bsky.social

A new study has identified a rare genetic condition which causes individuals to age at a faster rate than normal, shining a light on the mechanisms of aging. This study was jointly supervised by Kevin Myant, Elaine Dzierzak, Martin Reijns, @sproullab.bsky.social and Andrew Jackson edin.ac/4vDOCfM

edin.acRare ageing disorder links ‘biological clock’ to disease | Institute of Genetics and Cancer | Institute of Genetics and CancerScientists have discovered a rare genetic condition which causes people to age at a much faster rate, offering fresh insights into the ageing process.

@dansarni.bsky.social

What if DNA methylation changes aren’t just ticking of our biological clock but rather the rust breaking the gears? Very excited to share our work - how DNA methylation contributes to stem cell dysfunction and aging, published in @natgenet.nature.com doi.org/10.1038/s415... #epigenetics #aging 1/11

doi.orgA progeria syndrome links DNA hypermethylation to age-related pathology - Nature GeneticsThis study investigates the consequences of hypermethylation in a progeria syndrome caused by gain-of-function DNMT3A mutations, finding effects on adult stem cell function.

@dansarni.bsky.social

🚨 For a quick overview of our work, please also check out this research briefing 🚨 doi.org/10.1038/s415...

doi.orgTaking apart the DNA-methylation clock with an epigenetic progeria syndrome - Nature GeneticsWith advancing age, clock-like DNA-methylation changes occur across the genome. Whether these changes are passenger events or drive pathology remains to be determined. Here we report a novel epigeneti...

@dansarni.bsky.social

What if DNA methylation changes aren’t just ticking of our biological clock but rather the rust breaking the gears? Very excited to share our work - how DNA methylation contributes to stem cell dysfunction and aging, published in @natgenet.nature.com doi.org/10.1038/s415... #epigenetics #aging 1/11

doi.orgA progeria syndrome links DNA hypermethylation to age-related pathology - Nature GeneticsThis study investigates the consequences of hypermethylation in a progeria syndrome caused by gain-of-function DNMT3A mutations, finding effects on adult stem cell function.

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@dansarni.bsky.social

In our work we established HESJAS as a novel epigenetically driven accelerated aging syndrome that connects age-related DNA methylation gains with adult stem cell dysfunction and tissue decline. Suggesting that DNA methylation gains seen in aging could drive at least some aspects of it 10/11

@dansarni.bsky.social

This work is truly the result of a team effort and there are many people to thank at @uoe-igc.bsky.social and beyond. But it could not have been possible without Grainne Neary, Paula Carroll, Martin Reijns, @sproullab.bsky.social and Andrew Jackson 11/11

@dansarni.bsky.social

What if DNA methylation changes aren’t just ticking of our biological clock but rather the rust breaking the gears? Very excited to share our work - how DNA methylation contributes to stem cell dysfunction and aging, published in @natgenet.nature.com doi.org/10.1038/s415... #epigenetics #aging 1/11

doi.orgA progeria syndrome links DNA hypermethylation to age-related pathology - Nature GeneticsThis study investigates the consequences of hypermethylation in a progeria syndrome caused by gain-of-function DNMT3A mutations, finding effects on adult stem cell function.

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@dansarni.bsky.social

Loss of PAX5 is known to cause a pro B-cell block. We saw that PAX5 methylation led to its impaired activation in early immature B-cells. Interestingly, the few mature B-cells removed most of the methylation, suggesting that increased methylation is likely to be at the root of this B-cell block 8/11

@dansarni.bsky.social

Gains of DNA methylation at Polcomb regions are common in human aging. We find that the gains seen in HESJAS mirror this aspect of aging, and devised a clock based on HESJAS DNA methylation gains. Notably, we didn’t see other methylation changes associated with aging such as hypomethylation 9/11

@dansarni.bsky.social

What if DNA methylation changes aren’t just ticking of our biological clock but rather the rust breaking the gears? Very excited to share our work - how DNA methylation contributes to stem cell dysfunction and aging, published in @natgenet.nature.com doi.org/10.1038/s415... #epigenetics #aging 1/11

doi.orgA progeria syndrome links DNA hypermethylation to age-related pathology - Nature GeneticsThis study investigates the consequences of hypermethylation in a progeria syndrome caused by gain-of-function DNMT3A mutations, finding effects on adult stem cell function.

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@dansarni.bsky.social

But why does replacing one repressive mark (Polycomb deposited H3K27me3) with another (DNA methylation) causes these phenotypes? We reasoned that silencing by DNA methylation is less dynamic than chromatin repression affecting timely activation of key transcription factors 6/11

@dansarni.bsky.social

Focusing on haematopoiesis to understand the cause of lymphopenia, we found haematopoietic stem cells dysfunction resulting in a pro B-cell block. These stem cells showed DNA methylation gains at the PAX5 promoter, an essential transcription factor for B-cell development 7/11

@dansarni.bsky.social

What if DNA methylation changes aren’t just ticking of our biological clock but rather the rust breaking the gears? Very excited to share our work - how DNA methylation contributes to stem cell dysfunction and aging, published in @natgenet.nature.com doi.org/10.1038/s415... #epigenetics #aging 1/11

doi.orgA progeria syndrome links DNA hypermethylation to age-related pathology - Nature GeneticsThis study investigates the consequences of hypermethylation in a progeria syndrome caused by gain-of-function DNMT3A mutations, finding effects on adult stem cell function.

View full thread

@dansarni.bsky.social

HESJAS is caused by gain-of-function mutations in DNMT3A leading to its mislocalization and gains of DNA methylation at Polycomb marked DNA methylation valleys. We noted that patients with HESJAS also have ageing related pathologies 4/11

@dansarni.bsky.social

We established a mouse model that recapitulated many of the same phenotypes including growth retardation, lymphopenia and osteopenia. Interestingly, multiple tissues in these mice showed DNA methylation gains at Polycomb marked regions even before the appearance of age related symptoms 5/11

@dansarni.bsky.social

What if DNA methylation changes aren’t just ticking of our biological clock but rather the rust breaking the gears? Very excited to share our work - how DNA methylation contributes to stem cell dysfunction and aging, published in @natgenet.nature.com doi.org/10.1038/s415... #epigenetics #aging 1/11

doi.orgA progeria syndrome links DNA hypermethylation to age-related pathology - Nature GeneticsThis study investigates the consequences of hypermethylation in a progeria syndrome caused by gain-of-function DNMT3A mutations, finding effects on adult stem cell function.

@dansarni.bsky.social

Aging is multifactorial, characterised by multiple hallmark processes, such as DNA methylation changes. These changes have even been used as epigenetic clocks to predict biological age. However, whether they are passenger events or drivers of age-associated pathology is unknown 2/11

@dansarni.bsky.social

So how can we isolate DNA methylation changes from other age-related factors to study their potential role in aging? To this end we used a rare monogenic disorder, Heyn-Sproul-Jackson (HESJAS), to pave a direct path between a gene, its function and phenotype 3/11

Dan Sarni reposted

@sproullab.bsky.social

We've been awarded a UKRI MRC grant to examine the causes and consequences of #heterochromatin hypomethylation in cancer 🥳. #postdoc opportunity coming in the near future. #epigenetics. Please share with anyone who might be interested.

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