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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

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Lucas Farnung

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75,981 Aufrufe • vor 1 Jahr •via X (Twitter)

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Profilbild von Lucas Farnung
Lucas Farnungvor 1 Jahr

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.

Profilbild von Lucas Farnung
Lucas Farnungvor 1 Jahr

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.

Profilbild von Lucas Farnung
Lucas Farnungvor 1 Jahr

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

Profilbild von Lucas Farnung
Lucas Farnungvor 1 Jahr

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.

Profilbild von Lucas Farnung
Lucas Farnungvor 1 Jahr

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

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Squibler_vor 1 Jahr

📖 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!

Profilbild von AlbertW_lab
AlbertW_labvor 1 Jahr

@MarkertJon Beautiful work - congratulations Lucas and team!

Profilbild von Arne
Arnevor 1 Jahr

@MarkertJon Congratulations 🎊, Lucas!

Profilbild von Lucas Farnung
Lucas Farnungvor 1 Jahr

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

Profilbild von Ella Marushchenko
Ella Marushchenkovor 1 Jahr

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

Profilbild von Adeptus MAGAnicus
Adeptus MAGAnicusvor 1 Jahr

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

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