This work would have been impossible without my amazing co-authors @USchoeberl and Johanna Fitz or without the insightful supervision of Rushad Pavri. This work was supported by @IMPvienna and many fantastic collaborators. (Fin).

Take-home message: Antibody maturation is made possible through a dynamic, multiway chromatin hub that can be maintained without cohesin, and where SHM and CSR coexist. (9/10)

And most intriguingly: CSR activation didn’t disrupt SHM. The V region kept interacting with enhancers, and SHM & transcription remained stable. So CSR and SHM can occur not competitively, but cooperatively. (8/10).

Further, the new loops also did not decrease V-region transcription or SHM. This is super interesting, because it suggests that CSR and SHM are not competitive - a question that has been discussed for a long time. (7/10).

When we activated an IGH switch region (γ1), it was recruited into the hub. This is essential for CSR. Even without cohesin, this recruitment still occurred. So: loop extrusion isn’t required for enhancer-promoter contact or switch region activation. (6/10)

Here’s the twist: Cohesin depletion did not disrupt active transcription or the hub structure. This suggests other mechanisms are sufficient to maintain the hub. (5/10).

Using Tri-C, which maps multiway DNA contacts, we mapped the 3D folding of the human IGH locus during SHM. We discovered a multiway chromatin hub: The V region simultaneously contacts all its major enhancers, clustering them into one regulatory hub. (4/10)

But how are these processes organized in 3D at the complex human IGH locus? How are these structures formed and maintained? Does it require loop extrusion via cohesin? Can SHM and CSR coexist, or do they compete for access? We wanted answers. (3/10).

Background: SHM introduces mutations into the V region of the IGH locus, fine-tuning antibodies for higher affinity towards antigens. CSR lets B cells change antibody isotypes (classes) and redirect immune signaling. (2/10)

New Paper! .How do human B cells use dynamic DNA topology during antibody maturation? Our research published in @MolecularCell reveals how somatic hypermutation (SHM) and class switch recombination (CSR) work in the context of a regulated multiway 3D chromatin hub. (1/10) 🧵.

RT @MolecularCell: Online Now: Regulation of somatic hypermutation by higher-order chromatin structure https://t.co….