Kyle Eagen

Thanks, Rachel!

Link to the preprint here: www.biorxiv.org/content/10.6...

Thanks for catching that. Here it is! www.biorxiv.org/content/10.6...

10/ Check out the preprint for much more! Huge thanks to Yi-Hung, John, Krupa, and all other co-authors for their dedication to the project! We appreciate funders NIH, CPRIT, Alex’s Lemonade Stand, and @thewelchfoundation.bsky.social for supporting this work!

9/ By combining chromatin structural analyses in fusion-positive and fusion-negative cells, we uncover NSD3 as an adaptor protein for chromatin contacts. Our approach highlights how studies of chromosome misfolding in a rare cancer informs upon chromosome folding more broadly.

8/ Surprisingly, inactivating the PWWP domain also caused NSD3short to redistribute on chromatin, forming large domains. We find no evidence of interactions between these domains. This identifies a separation-of-function mutant that uncouples chromatin occupancy from chromatin interactions.

7/ Inactivating the PWWP domain with a point mutation (W284A) impairs NSD3short’s ability to promote chromatin contacts.

6/ Does NSD3 have an analogous role in fusion-naïve cells? Yes! The short isoform of NSD3, NSD3short (HiBiT-tagged), promotes chromatin contacts when expressed in fusion-negative cells. NSD3short contacts are longer than CTCF-CTCF loops and form in the A compartment.

5/ NSD3 also stabilizes chromatin contacts between BRD4-NUT chromatin domains. Depletion of NSD3 decreases chromatin contacts both in cis and in trans.

4/ Depletion of NSD3 shows that NSD3 deposits H3K36me2 at BRD4-NUT-bound loci, stabilizes BRD4-NUT on chromatin, and stabilizes BRD4-NUT condensates.

3/ Based on proteomics data, NSD3, itself a NUT fusion partner, interacts with BRD4-NUT. NSD3 is a histone H3K36 methyltransferase. Consistent with this, NSD3 and H3K36me2 are enriched with BRD4-NUT on chromatin and NSD3 is enriched in BRD4-NUT condensates.

2/ Previously, we discovered that the BRD4-NUT fusion oncoprotein drives distant chromatin interactions between oncogenes. We wondered, what are the cofactors of BRD4-NUT-driven chromatin regulation? And, do such factors have analogous functions in fusion-naïve cells?

1/ Excited to share a new preprint from the lab! We identify NSD3 as a novel regulator of chromatin 3D structure. 🧵

Interphase chromosome conformation is specified by distinct folding programmes inherited through mitotic chromosomes or the cytoplasm Nature Cell Biology - Schooley et al. find that mitotically bookmarked loci drive a transient chromosome folding state during G1 entry that is subsequently modulated by factors inherited through...

Happy to share that my postdoc work with @jobdekker.bsky.social is out!
rdcu.be/eWHD2

We characterize interphase chromatin folding programs with distinct modes of mitotic inheritance and identify the chromosome-intrinsic capacity to form a microcompartment of active CREs during mitotic exit.

Inheriting chromosome conformation - Nature Cell Biology Chromosomes unfold and refold each time cells divide. A study by Schooley et al. demonstrates that chromosome-intrinsic and cytoplasmic factors uniquely contribute to interphase chromosome structure, ...

Check out the News & Views by @kyleeagen.bsky.social : www.nature.com/articles/s41...

Dynamics of microcompartment formation at the mitosis-to-G1 transition - Nature Structural & Molecular Biology Goel et al. produce high-resolution three-dimensional genome structure mapping from mitosis to G1 phase to show unseen interactions between enhancers and promoters in prometaphase. Polymer modeling in...

Be sure to also check out the great paper from @andersshansen.bsky.social and colleagues where they discover microcompartments on mitotic chromosomes using Region Capture Micro-C. Exciting times for those interested in chromosome conformation during cell division!
www.nature.com/articles/s41...

Interphase chromosome conformation is specified by distinct folding programmes inherited through mitotic chromosomes or the cytoplasm - Nature Cell Biology Schooley et al. find that mitotically bookmarked loci drive a transient chromosome folding state during G1 entry that is subsequently modulated by factors inherited through the cytoplasm.

Kudos to all authors for a fascinating story! They discover new aspects of chromosome folding as cells exit mitosis, including two folding programs that establish interphase conformation and microcompartmentalization of mitotically bookmarked cis-regulatory elements.
www.nature.com/articles/s41...

Inheriting chromosome conformation - Nature Cell Biology Chromosomes unfold and refold each time cells divide. A study by Schooley et al. demonstrates that chromosome-intrinsic and cytoplasmic factors uniquely contribute to interphase chromosome structure, with new possibilities for how gene expression programs are passed from mother cells to daughter cells.

Excited to share a News & Views highlighting a new, excellent paper from @jobdekker.bsky.social and @allanaschooley.bsky.social!
www.nature.com/articles/s41...

Dynamics of microcompartment formation at the mitosis-to-G1 transition - Nature Structural & Molecular Biology Goel et al. produce high-resolution three-dimensional genome structure mapping from mitosis to G1 phase to show unseen interactions between enhancers and promoters in prometaphase. Polymer modeling in...

See this recent paper by @andersshansen.bsky.social that discovers similar microcompartmentalization during mitotic exit:

www.nature.com/articles/s41...

Inheriting chromosome conformation - Nature Cell Biology Chromosomes unfold and refold each time cells divide. A study by Schooley et al. demonstrates that chromosome-intrinsic and cytoplasmic factors uniquely contribute to interphase chromosome structure, ...

And also see this nice News and Views by @kyleeagen.bsky.social

www.nature.com/articles/s41...

Interphase chromosome conformation is specified by distinct folding programmes inherited through mitotic chromosomes or the cytoplasm - Nature Cell Biology Schooley et al. find that mitotically bookmarked loci drive a transient chromosome folding state during G1 entry that is subsequently modulated by factors inherited through the cytoplasm.

Exciting new paper out! @allanaschooley.bsky.social and Sergey Venev led this project that let to the discovery of two chromosome folding programs: one inherited via mitotic chromosomes and one mitotic inherited through the cytoplasm!

www.nature.com/articles/s41...

Congrats Josh, Peggy, Gandhar, Elmira, and team!!!

Our new preprint 🧬🔗 www.biorxiv.org/content/10.1...
BRD4-NUT forms liquid-like condensates that locally constrain nucleosomes via BRD4-mediated crosslinking— physical control of #chromatin by #LLPS transcription condensates. @semeigazin.bsky.social @katsuminami.bsky.social @masaashimazoe.bsky.social

Congrats, Bruno!

Congratulations, Liling! A very exciting project!

Thrilled to share our new work on #aging in the murine hematopoietic system! There is a lot here- stem cell numbers, self-renewal rates, mutation rates, mutation signatures, clonal fitness, environmental effects...

In lab’s #FIRSTPREPRINT, we present methods to measure nanometer-scale organization around & between specific proteins in condensates in live cells. We uncover unexpected heterogeneity for a liquid-like phase with local meshwork spanning 10-50nm, stemming from ribosome biogenesis in the nucleolus.