Christian Nefzger
@nefzgerlab.bsky.social
Cell identity/Transcription factors/Aging/Maturation - Group Leader/PI at the IMB, University of Queensland, Brisbane, Australia
Could you add me too :)
November 27, 2024 at 8:32 AM
Could you add me too :)
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
November 25, 2024 at 9:58 AM
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
bsky.app/profile/nefz...
Dear Jalees, thanks for promoting our recent study :)
Dear Jalees, thanks for promoting our recent study :)
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
Thread 🧵👇1/9
Link: doi.org/10.1016/j.cmet.2024.06.006
Thread 🧵👇1/9
November 25, 2024 at 2:09 AM
bsky.app/profile/nefz...
Dear Jalees, thanks for promoting our recent study :)
Dear Jalees, thanks for promoting our recent study :)
🙏 Chris! I LOVE your own work in the AP-1 space 💛
November 24, 2024 at 8:26 AM
🙏 Chris! I LOVE your own work in the AP-1 space 💛
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 😊
November 24, 2024 at 7:38 AM
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 😊
Dear William, could you possibly add me. Thanks
November 20, 2024 at 8:13 AM
Dear William, could you possibly add me. Thanks
Hi Patrick, if possible, could you add me to the list. Thanks
November 20, 2024 at 7:00 AM
Hi Patrick, if possible, could you add me to the list. Thanks
Dear Çağrı, could you possibly add me to the pack?
November 18, 2024 at 9:14 PM
Dear Çağrı, could you possibly add me to the pack?
Dear Oliver, could you possibly add me to this pack?
November 18, 2024 at 1:00 PM
Dear Oliver, could you possibly add me to this pack?
Dear Angelo, could you possibly add me to the starter pack?
November 18, 2024 at 12:33 PM
Dear Angelo, could you possibly add me to the starter pack?
Dear Tatiana, could you add me to the Geroscience starter pack? Many thanks :)
November 18, 2024 at 11:24 AM
Dear Tatiana, could you add me to the Geroscience starter pack? Many thanks :)
Could you please add me to this one :)
November 18, 2024 at 11:19 AM
Could you please add me to this one :)
Could you please add me to the starter pack too :) Thanks heaps
November 18, 2024 at 11:19 AM
Could you please add me to the starter pack too :) Thanks heaps
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...
doi.org/10.1016/j.cm...
November 18, 2024 at 11:01 AM
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...
doi.org/10.1016/j.cm...
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.
November 18, 2024 at 10:20 AM
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.
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.
November 18, 2024 at 10:20 AM
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.
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.
November 18, 2024 at 10:15 AM
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.
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
November 18, 2024 at 10:14 AM
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
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.
November 18, 2024 at 10:13 AM
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.