7/
Huge thanks to all co-authors for this team effort:
💡 Fabio, @xxxmichixxx.bsky.social , Lucas, Jennifer, Eliza, Daniel & @marcbuhler.bsky.social
Check out their work too – great scientists and wonderful collaborators!
2/ CHD4 is essential, HP1 is not
We generated mESCs where ADNP can no longer bind CHD4 or HP1.
Only CHD4 loss leads to transposon activation and CTCF gain at SINE B2 elements.
We also endogenously fused catalytically dead CHD4 to ADNP.
CHD4’s remodeling activity is crucial for repression.
4/ A new paradigm
Most remodelers transiently associate with TFs.
But ChAHP is stable and sequence-specific.
ADNP targets CHD4 to specific loci → CHD4 remodels chromatin → TF access blocked.
A refined mechanism for chromatin control!
3/ Remodeling, not roadblocking
Catalytically inactive ChAHP still binds chromatin (even more strongly!), but fails to repress transposons or antagonize CTCF.
So, remodeling – not steric competition – is key.
Josip Ahel
1/ ChAHP: A special chromatin complex
ChAHP = CHD4 + ADNP + HP1.
Previously, we showed it represses retrotransposons and limits CTCF binding.
But how it does so was unclear.
Now, we dissect ChAHP in mouse stem cells using precise genome editing
🧵 New preprint!
How does a chromatin remodeler know where to act?
In our latest study, we show how the transcription factor ADNP targets CHD4 remodeling activity to silence transposons and block CTCF.
👇 A thread on the ChAHP complex and how it weaves chromatin
🧬🔬🧵
www.biorxiv.org/content/10.1...
6/ TL;DR
🔹 CHD4 is the effector of ChAHP
🔹 Remodeling – not just binding – is required to repress SINEs & evict CTCF
🔹 ADNP directs CHD4 to specific loci
#Epigenetics #Chromatin #Transposons #CTCF
5/ Curious to hear why SINE transcription is specifically affected?
Check out our companion preprint by @jakobschnabl.bsky.social , Fabio, and @xxxmichixxx.bsky.social :
📘 bsky.app/profile/jako...
📄 www.biorxiv.org/content/10.1...
#RNApolIII #TFIIIB #Transcription #Retrotransposons
Josip Ahel
Josip Ahel
Josip Ahel
📖 Happy to share our recent preprint! www.biorxiv.org/content/10.1... We discovered how SINEs are kept silent: the ChAHP protein complex acts as a molecular brake on POL III transcription retrotransposons. A 🧵:
The application deadline has been extended for a postdoc position in our lab until August 22. Please enquire/apply if you are interested in ADP-ribosylation, ubiquitination, genome stability or immunity.
my.corehr.com/pls/uoxrecru...
Transcription in eukaryotes is regulated by chromatin-based mechanisms that control nucleosome occupancy, chromatin modifications, and transcription factor binding. We have previously shown that the transcription factor ADNP forms the ChAHP complex with the chromatin remodeler CHD4 and HP1 proteins, acting as a site-specific regulator of transcription and antagonist of CTCF binding. However, the molecular basis of these functions remained unclear. Here, we demonstrate that the CHD4 subunit is essential to antagonize CTCF and silence transcription of transposons, while HP1 proteins are dispensable. Although the remodeling activity of CHD4 is not required for ChAHP chromatin association, it is critical for both transposon repression and CTCF antagonism. Our findings support a model wherein ADNP recruits chromatin remodeling activity in a sequence-specific manner, enabling transcriptional control and local modulation of chromatin architecture. ### Competing Interest Statement The Friedrich Miescher Institute for Biomedical Research (FMI) receives significant financial contributions from the Novartis Research Foundation. Published research reagents from the FMI are shared with the academic community under a Material Transfer Agreement (MTA) having terms and conditions corresponding to those of the UBMTA (Uniform Biological Material Transfer Agreement). Novartis Research Foundation, n.a. Swiss National Science Foundation, grant 310030_188835
Short interspersed nuclear elements (SINEs) are abundant non-autonomous transposable elements derived from RNA polymerase III (POL III)-transcribed short non-coding RNAs. SINEs retain sequence feature...
