iiinova — where your digital self keeps evolving

Reposted by Júlia Bonjoch

David Landeira @davidlandeira.bsky.social · 10/09/2025

Thrilled to share our story in its final form! nature.com/articles/s41... 💥 After ~10 years, we show that BMAL1 represses transposons via chromatin regulation in embryonic stem cells—rather than circadian rhythms as in adult tissues.

nature.com

1187

Reposted by Júlia Bonjoch

Sara Wickstrom @sarawickstrom.bsky.social · 12/09/2025

My lab @mpi-muenster.bsky.social is looking for a computational biologist with a passion for imaging and spatial biology. A staff scientist position with long-term perspective! Apply and spread the word 🙏 jobs.mpi-muenster.mpg.de/jobposting/0...

jobs.mpi-muenster.mpg.de

Computational image analyst (m/f/d)

The Max Planck Institute for Molecular Biomedicine in Münster, Germany, has an opening for a

18685

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

Thanks for all the support and discussions, Sara!

010

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

20/ Biostatistics/Bioinformatics IRB facility scientists from @irbbarcelona.org + best colleagues and friends Paloma Solá @guiomarsolanas.bsky.social @circatom.bsky.social @aznarbenitahlab.bsky.social

050

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

19/ Thanks for making it until the end! Last but not least, most special thanks go to all the people who helped this project finally make it to a written article, including our mechanobiology expert collaborators @sarawickstrom.bsky.social @katemiro.bsky.social +

130

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

18/ During ageing, following YAP activation, BMAL1-YAP complex is directed to enhancers of inflammation genes, many of which are regulated by p65. All this leads to an increase in expression of these genes, contributing to the transcriptional rewiring of epid cells during ageing.

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

17/ Finally, based on all the above-mentioned results, we propose the following molecular mechanism: In adult epidermis, during homeostatic conditions, BMAL1 and YAP coordinately bind to enhancers of identity and maintenance genes.➕

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

16/ Now, a more detailed p65 genomic occupancy analysis revealed the presence of p65 in promoters and TSSs of up-regulated inflammation-related genes, some of which present BMAL1-YAP bound enhancers.

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

15/ We consistently found p65-NF-kB binding sites enriched in active enhancers bound by BMAL1 and YAP in aged epidermis. Actually, we have already shown in a previous study that p65 plays a key role in controlling the expression of inflammation genes during epidermal ageing!👀

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

14/ What’s more, some of the up-regulated inflammation-related genes that were BMAL1 or YAP targets in adult epidermis, gain BMAL1-YAP binding in their enhancers with age.

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

13/ What about BMAL1-YAP complex? Indeed, when we compare both TFs ChIP-seq data, we observe a stat significant genomic overlap between the two TFs. + Notably, during ageing, this happens in active enhancers of inflammation genes, some of which expression is up-regulated.

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

12/ These suggest that, in addition to mechanical changes of the skin, pro-inflammatory cues act as a second signalling layer that leads to ageing-associated YAP activation. 👯

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

11/ Yes! We show that a non-canonical YAP activation through phosphorylation of Tyr357 is increased in the aged epidermis, and that this activation is reduced upon anti-inflammatory treatment with anti-IL17 blocking antibodies.

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

10/ Using a Col14KO mouse to model skin ageing mechanics, we unveiled that YAP activation through mechanotransduction signalling alone is not enough to recapitulate YAP aged binding to inflammation genes. So, are there other triggers that can boost YAP activation during ageing?

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

9/ Could YAP activation be involved in BMAL1 genomic location rewiring to inflammation-related genes we observe during ageing? To tackle that, we first needed to gain a little insight into how YAP activation happens during ageing. ⤵️

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

8/ However, during ageing, YAP gains binding to inflammation-related genes, similar to what we see for BMAL1. In fact, BMAL1 binding sites are enriched exclusively in aged YAP peaks located in active enhancers.😮

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

7/ In vivo ChIP-seq analysis of YAP in the epidermis confirmed its well-known role as a mechanotransduction TF, as its genomic occupancy is enriched in mechanics- and Hippo-related genes.🦛

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

6/ Other groups have underscored that changes in tissue mechanics occur during ageing. In the IFE, we observed an increased stiffness of the BM during ageing, and this correlates with an increased proportion of epidermal cells positive for the Hippo-dependent active YAP.❗️

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

5/ TF motif enrichment analysis of BMAL1 peaks in active enhancers revealed TEAD binding sites. PLA assay on skin sections shows BMAL1-YAP interactions in the nucleus of epidermal cells, suggesting a possible BMAL1 and YAP functional interaction in the epidermis chromatin.🧐

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

4/ In addition, we also see that BMAL1 binding is not restricted to rhythmically expressed genes, supporting a non-canonical BMAL1 function as a transcription factor beyond its role in the circadian clock.😈

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

3/ In vivo ChIP-seq revealed BMAL1 binding to be enriched in inflammation genes in the aged epidermis, while during adulthood, this binding is more restricted to homeostatic genes. Moreover, this binding occurs in enhancers, emphasising BMAL1 role in enhancer regulation.

100

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

2/ By performing a comprehensive analysis of DEGs throughout 24 hours in adult and aged murine epidermis, we reveal a list of more than 100 up-regulated genes during ageing associated with inflammation functions. But who promotes such an expression program?

110

Júlia Bonjoch @juliabonjoch.bsky.social · 23/04/2025

Hi Bluesky community:) Our new manuscript is now available as a preprint!⛅️ biorxiv.org/content/10.1... 1/ Here, we describe a novel BMAL1-YAP complex in epidermal cells, which is hijacked during ageing to control the expression of up-regulated inflammation genes through enhancer binding.🧵

biorxiv.org

BMAL1 and YAP cooperate to hijack enhancers and promote inflammation in the aged epidermis

Ageing is characterised by persistent low-grade inflammation that is linked to impaired tissue homeostasis and functionality. However, the molecular mechanisms driving age-associated inflammation rema...

2215

Reposted by Júlia Bonjoch

guiomarsolanas.bsky.social @guiomarsolanas.bsky.social · 23/04/2025

🌟 Excited to share that our latest preprint is now available! We’re one step closer to understanding the complex mechanisms behind ageing and inflammation. 👉 Read the preprint here: www.biorxiv.org/cgi/content/... Thank you to everyone who supported and believed in this project along the way!

biorxiv.org

BMAL1 and YAP cooperate to hijack enhancers and promote inflammation in the aged epidermis

111

Reposted by Júlia Bonjoch

Jacob Smith @jacobsmithsci.bsky.social · 03/01/2025

🧪 ✍️ Please check out our new review on intercellular and interorgan communication between circadian clocks ⏰🧬 out today in Nature Reviews Molecular Cell Biology 🎉 @natrevmcb.bsky.social ! Here is the SharedIt link for free access: rdcu.be/d5ppE

rdcu.be

Circadian clock communication during homeostasis and ageing

Nature Reviews Molecular Cell Biology - Communication between the circadian clocks of different cell and tissue types supports the daily rhythms of homeostatic processes that maintain bodily...

32710