Escape from X inactivation is directly modulated by Xist noncoding RNA Nature Cell Biology - The authors show that increased Xist RNA levels can induce de novo silencing of genes that normally escape X inactivation. SPEN depletion prevents the silencing of escape...

Very happy to share our paper rdcu.be/eUImj out today in @natcellbio.nature.com 🎉🎉🎉
We uncover an unexpected role for endogenous Xist RNA in regulating X-linked genes that escape X-inactivation.

📣 Yesterday our study uncovering the ancestry bias in gene annotations was finally published in @natcomms.nature.com!
www.nature.com/articles/s41...

If you work in human genetics or transcriptomics, do not miss our tweetorial!👇

@guigolab.bsky.social @bsc-cns.bsky.social @crg.eu

Giving a seminar today @ethz.ch on our new X-reactivation findings during aging—back at the institute where I started my PhD 10 years ago. Can’t wait to see some familiar faces!

Poster advertising the 6th X-inactivation meeting from Oct 19-23 2026 in Sapporo, Japan. The organizers are Asato Kuriowa, Edda Schulz, Ikuhiro Okamoto, Rafael Galupa, Takashi Sado, Mitinori Saitou.

📣 SAVE THE DATE
Next X-inactivation meeting in Sapporo, Japan, 19-23 October 2026. Visit x-inactivation-meeting.org to join our mailing list. 🧬 speakers @dandergassen.bsky.social @marnieblewitt.bsky.social @heard65.bsky.social @crougeulle.bsky.social @sexchrlab.bsky.social @zhouqi1982.bsky.social

This work, led by Lison Lemoine and co-authors @sarahhoelzl.bsky.social, @hasenbeint.bsky.social and Elisabeth Graf @tum.de, has been published today in Scientific Reports: www.nature.com/articles/s41...

This workflow provides a powerful and accessible framework for studying allele-specific transcript diversity, highlighting the mechanistic insights made possible by long-read transcriptomic data.

We explored imprinted loci, known for allele-specific coding and non-coding isoforms, and successfully benchmarked historical findings. Our approach also uncovered isoforms expressed from both the active and inactive X chromosomes of escape genes in females.

New paper from the lab: we’re using long-read sequencing to disentangle isoform complexity at allele-specific loci 🧬💡
Here, we combine the PacBio Iso-Seq workflow with the established WhatsHap phasing approach to assign long reads to the correct allele in polymorphic F1 mouse hybrids.

Thank you 🔥

Allelome.LINK/02_resource at main · AndergassenLab/Allelome.LINK Contribute to AndergassenLab/Allelome.LINK development by creating an account on GitHub.

All mouse (6 major organs) and human (54 GTEx tissues) lncRNA-to-target predictions are easily accessible for visual inspection, allowing researchers to select candidates based on target and mechanism predictions
GitHub IGV resource link: github.com/AndergassenL...

Importantly, as more individual sequencing data and risk variants become available, we anticipate that this strategy will continue to elucidate targets and mechanisms, ultimately decoding the entire cis-acting landscape of the non-coding genome.

We applied the strategy to mouse organs and to the largest allele-specific human dataset @gtexportal.bsky.social, including 54 tissues from nearly 1000 individuals. Given the high genetic diversity in humans, each individual allows for the discovery of new allelic correlation events.

By further integrating H3K27ac data, we showed that the same principle can be used to link enhancers and other cis-acting DNA regulatory elements to their corresponding targets!

The strategy is simple: A repressive lncRNA-to-target prediction occurs when the lncRNA and nearby protein-coding genes show opposite allele-specific expression biases, while an enhancing interaction occurs when both show allelic expression bias toward the same allele.

Allele-specific genomics decodes gene targets and mechanisms of the non-coding genome Abstract. A large proportion of disease variants is found in non-coding RNAs (ncRNAs), gene loci that have been identified as key regulatory elements. Howe

This work, led by @hasenbeint.bsky.social and co-authors @sarahhoelzl.bsky.social, Stefan Engelhardt at the @tum.de #TRR267, has been published in @narjournal.bsky.social

link: doi.org/10.1093/nar/...

Yes! The Allelome.LINK framework integrates allele-specific transcriptomics and/or epigenomics to connect cis-acting lncRNAs and enhancers with their nearby protein-coding targets, thereby linking overlapping non-coding disease variants to the genes they affect.

Cracking the code of the non-coding genome via allele-specific genomics?
Can we link non-coding elements—like lncRNAs and enhancers—to their protein-coding target genes, and in doing so, connect overlapping non-coding disease variants to their protein-coding counterparts?

tRNA-overlapping long non-coding RNA loci repress codon-biased genes Ahmed et al. define tRNA-overlapping lncRNAs (tROLs). tROLs in gene-dense regions interact between chromosomes and depend on each other’s transcription. tROL perturbations silence codon-biased genes i...

📢 Paper Alert: tinyurl.com/yzy2d864. We characterized tRNA-overlapping lncRNA loci = tROLs! tROL perturbations silence
codon-biased genes in inter-chromosomal proximity. tROLs bridge the non-coding
and coding genomes. @sickkidsto.bsky.social @uoftpress.bsky.social

A male-essential miRNA is key for avian sex chromosome dosage compensation - Nature Birds have evolved a unique sex chromosome dosage compensation mechanism involving the male-biased microRNA (miR-2954), which is essential for male survival by regulating the expression of dosage-sens...

Our study on a male-essential microRNA and the evolution of other dosage compensation mechanisms in birds is now out in Nature! www.nature.com/articles/s41...

🗞️Our June issue is live!📷 This month, we're featuring work on editing epigenetic age, somatic mutation, senescence, Alzheimer’s biomarkers and much more. Read it all here: nature.com/nataging/vol...

We are so happy to be on the cover @sarahhoelzl.bsky.social 🎉 The cover depicts the Three Fates, who manipulate the threads of life and death. The Fates are shown as three older women, unraveling the threads of the inactive X chromosome during aging. www.nature.com/nataging/vol...

Silent X chromosome awakens with age In aging female mice, genes on the second X chromosome become active again. This could be an explanation for sex differences in aging humans regarding disease.

Why do women experience aging-related diseases differently than men? A new study shows that with age, genes on the inactive X chromosome can reactivate – potentially influencing conditions like #dementia and #autoimmunity: go.tum.de/987255

#genetics #aging

📷 @dandergassen.bsky.social

Divergent DNA methylation dynamics in marsupial and eutherian embryos - Nature A study reports on the DNA methylation dynamics during embryogenesis in marsupials, showing that these differ from those occurring during embryogenesis in eutherian mammals.

We're excited to publish our latest study led by Bryony Leeke @bryonyleeke.bsky.social and Wazeer Varsally, now out in @nature.com 🍾This study focusses on the epigenome of marsupial embryos 🦘 mapping DNA methylation in embryo development to specific embryo events www.nature.com/articles/s41... 🧵

Our new contribution to the quest to find causal GWAS genes! Sam Ghatan from my lab at @nygenome.org led a systematic comparison of eQTLs and CRISPRi+scRNA-seq screens. TL;DR: they provide highly complementary insights, with ortogonal pros and cons. 🧵👇
www.biorxiv.org/content/10.1...

Long-read transcriptomics of a diverse human cohort reveals widespread ancestry bias in gene annotation Accurate gene annotations are fundamental for interpreting genetic variation, cellular function, and disease mechanisms. However, current human gene annotations are largely derived from transcriptomic...

Do you work in 💫human genetics💫?
Have you ever worried about what’s inside your gene annotation GTF⁉️

WELL, YOU SHOULD! 😱
Especially when studying a genetically diverse 🌍 cohort!

🔴We discover that gene annotations are European-biased 👉 impacting downstream analyses!

Don't miss this thread🧵⬇️
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X inactivation shows frail ends when mice age Nature Aging - Most genes on the inactive X chromosome are repressed throughout life, but there are exceptions. Hoelzl and colleagues map genes that escape repression in multiple organs over the...

Finally, we would like to thank all the reviewers for their valuable comments, the @nataging.nature.com editors, as well as Anton Wutz for highlighting our research in the News & Views section of Nature Aging: rdcu.be/eknAp

AgingX/02_resource at main · AndergassenLab/AgingX Contribute to AndergassenLab/AgingX development by creating an account on GitHub.

Overall, the escape landscape shows a high degree of organ and cell type specificity, with strong evidence of cluster organization. Explore the full Escape Atlas in the IGV browser for each organ and age time point: github.com/AndergassenL...

Since we find that several age-specific escapees are associated with human diseases, we propose that their elevated expression in females may contribute to sex-biased disease progression with age, offering a new mechanism for age-related sex differences beyond hormonal influence.

In addition, allele-specific single-cell analysis revealed that age-specific escape manifests within distinct cell types, further providing evidence that age-related epigenetic changes promote gene escape.

An intriguing example is Reps2, where a specific isoform escapes in an age-dependent manner. While the long isoform of Reps2 is expressed from the Xa, the promoter of the short isoform shows age-dependent biallelic activity, leading to Xi-specific expression of the short isoform.