Ever wondered how transcription choreographs histone modifications? Our work reveals the basis of co-transcriptional H3K36me3 by SETD2. We visualize how a histone writer coordinates with the transcription machinery! This is the magnus opus of Jon Markert

There is so much to see and learn: Using cryo-EM, we visualized 6 different RNA Pol II-DSIF-SPT6-PAF1c-TFIIS-IWS1-SETD2 complexes with nucleosomes, hexasomes, and FACT. These structures unveil how SETD2 interacts with both downstream & upstream nucleosomes during active txn.

SETD2 binds unwrapped nucleosomes via the catalytic SET domain & relies on interactions with SPT6. The SPT6 death-like domain (DLD) anchors SETD2, ensuring precise H3K36me3 deposition and relieves the auto-inhibitory domain of SETD2 to activate its methyltransferase activity.

Surprisingly, upstream nucleosomes appear to be SETD2's preferred substrates, highlighting a coordinated interplay between txn elongation and histone modification where SETD2 methylates the proximal and distal H3 of the upstream nucleosome, establishing the H3K36me3 landscape

And we elucidate more about SPT6 function: SPT6 not only facilitates SETD2 positioning through a unique interaction motif but also stabilizes exposed H2A–H2B dimers. This dual role of SPT6 cements its importance in chromatin transcription.

For more details, dive into our manuscript: tuned for more insights into chromatin biology and transcription dynamics. Feedback & questions welcome! @MarkertJon #Transcription #Epigenetics

📖 Still grinding on that book? That look says it all… 😏 Why struggle for months when you can finish in minutes? 💻✨ 👉 Get started with Squibler and write like a pro, fast!

@MarkertJon Beautiful work - congratulations Lucas and team!

@MarkertJon Congratulations 🎊, Lucas!

@MarkertJon Thank you, Arne. The story has come a long way from the time I presented at Einstein.

@MarkertJon Congratulations, Dr. Farnung & team! The role of SETD2 role in modifying upstream nucleosomes is amazing. Does this process vary between cell types?

@ScienceMagazine @MarkertJon I understand a few of these words!