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Christian Nefzger @nefzgerlab.bsky.social · Nov 27

Could you add me too :)

Christian Nefzger @nefzgerlab.bsky.social · Nov 25

Thanks for sharing the paper! Yes, we think AP-1 (with co-factors like Stat3) drives aging phenotypes like inflammaging. Various stimuli such as interleukins but also age-increased plasma factors like TGF-β (e.g. via tinyurl.com/4sdps2ty) can spike AP-1 activity (see Fig 6) & drive chromatin opening

Christian Nefzger @nefzgerlab.bsky.social · Nov 25

bsky.app/profile/nefz...
Dear Jalees, thanks for promoting our recent study :)

Christian Nefzger @nefzgerlab.bsky.social · Nov 18

Our recent study in Cell Metabolism provides compelling evidence that chromatin accessibility and transcription factor network remodeling in aging reflect the predictable degrading effects of a mechanism initially driving organismal maturation.
Link: doi.org/10.1016/j.cmet.2024.06.006
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Christian Nefzger @nefzgerlab.bsky.social · Nov 24

🙏 Chris! I LOVE your own work in the AP-1 space 💛

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Christian Nefzger @nefzgerlab.bsky.social · Nov 24

Dear Michael, apologies for missing this earlier. Fascinating linkages in fly aging in your study: inflammation possibly preceding Smurf transition, Smurf genes associated with immune/stress responses & downregulation of PRC2 components, among other findings. Always happy to chat - feel free to DM 😊

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Christian Nefzger @nefzgerlab.bsky.social · Nov 22

🙋🏼‍♂️

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Christian Nefzger @nefzgerlab.bsky.social · Nov 20

Dear William, could you possibly add me. Thanks

Christian Nefzger @nefzgerlab.bsky.social · Nov 20

Hi Patrick, if possible, could you add me to the list. Thanks

Christian Nefzger @nefzgerlab.bsky.social · Nov 18

Dear Çağrı, could you possibly add me to the pack?

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Reposted by Christian Nefzger

Shaun Mahony @shaunmahony.bsky.social · Nov 18

Really intriguing model of AP-1 driven aging.

@anshulkundaje.bsky.social @suragnair.bsky.social - thinking of your AP1-related results in the ChromBPNet paper here...

Christian Nefzger @nefzgerlab.bsky.social · Nov 18

8/9 🧵 Our study indicates that AP-1–linked chromatin opening drives organismal maturation by disrupting the activity of cell identity TFBS-rich early-life REs, thereby progressively shutting down developmental processes to reprogram the transcriptome towards adult tissue function.

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

Dear Oliver, could you possibly add me to this pack?

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

Dear Angelo, could you possibly add me to the starter pack?

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

Dear Tatiana, could you add me to the Geroscience starter pack? Many thanks :)

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

Could you please add me to this one :)

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

Could you please add me to the starter pack too :) Thanks heaps

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

We introduce the "Stimulus-Induced Programming Hijacks Ontogeny" (SIPHON) model based on compelling evidence that chromatin & transcription factor network remodeling in aging reflects the predictable degrading effects of a mechanism initially driving organismal maturation
doi.org/10.1016/j.cm...

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

🙏 to Manuel Serrano for writing a preview for our study @ Cell Metabolism. A pattern emerges in chromatin aging: AP-1 steals the show dlvr.it/TBvzgR

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

Thanks to Longevity Technology for writing an article about our recent study:
"Master controller of aging and development uncovered.
New insights into transcription factors and chromatin remodeling reveal potential for improving age-related health outcomes. #innovation #aging "
t.co/a8Mxgowkbe

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

Thanks to EpiGenie for an article about our study: "Christian Nefzger's lab reveals how chromatin remodeling driven by the AP-1 pioneer transcription factor supports cell maturation. Beware o' the mechanism pirated during #aging to induce the appearance of age-related phenotypes!" bit.ly/3zOqBux

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

9/9 🧵 In aging, this mechanism is hijacked by continued AP-1-driven chromatin opening, induced by stress and inflammation, further diminishing the activity of developmental gene regulatory elements which may underpin many of the predictable phenotypes linked to aging.

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

8/9 🧵 Our study indicates that AP-1–linked chromatin opening drives organismal maturation by disrupting the activity of cell identity TFBS-rich early-life REs, thereby progressively shutting down developmental processes to reprogram the transcriptome towards adult tissue function.

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

7/9 🧵 Such remodelling can be triggered by directly elevating AP-1 through overexpression or indirectly via metabolic stress or the age-increased systemic factor TGFβ. H3K27me3 depletion partially phenocopied AP-1 overexpression in support of a critical role of loss of epigenetic repression.

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

6/9 🧵 We show that redistribution of TFs to age-exposed AP-1-TFBS-rich REs, in synergy with mild down-regulation of cell identity TF expression drives accessibility loss of early-life REs and underpins age-altered gene expression

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

5/9 🧵 Early-life gene regulatory elements (REs) are engaged through cell type identity TFs and progressively loose accessibility during maturation & aging. Conversely REs gaining accessibility throughout life have fewer cell identity TFBS and rely on elevated activity of TF AP-1 for engagement.

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Christian Nefzger @nefzgerlab.bsky.social · Nov 18

4/9 🧵 By studying transcription factor binding site (TFBS) patterns in regions that open/close with age we found a common signature across cell types. Remarkably, by reanalyzing many previous data sets for organismal maturation (incl. human data spanning life-stages) we found the same TFBS pattern.

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