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Dykhuizen Lab @dykhuizenlab.bsky.social · 12/08/2026

A big thanks to the many people that helped with this project! This is the result of a VERY long-standing collaboration with the Wendt Lab and critical assistance from Epicypher, the Weake Lab, and the Tao Lab. Here's to many more discoveries together! (11/11)

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Dykhuizen Lab @dykhuizenlab.bsky.social · 12/08/2026

There are still lots of unanswered questions. A big one is, why is the majority of PBAF at open active promoters if it isn’t required for accessibility? But perhaps the bigger question is could PBRM1 be a therapeutic target for metastatic breast cancer ? Hopefully we figure that out next...(10/11)

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Dykhuizen Lab @dykhuizenlab.bsky.social · 12/08/2026

But still, only some of these genes were actually induced. Using the ATAC-Seq data of the promoters with PBRM1-dependent accessibility we identified consensus sequences for TFs important for EMT and metastasis including ATF3, IRF1, and SNAIL, which were co-bound with PBAF at many sites. (9/11)

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Dykhuizen Lab @dykhuizenlab.bsky.social · 12/08/2026

We found that PBAF can be enriched from lysates with H3K14Ac peptides and more acetylations helps. Epicypher used modified nucleosomes and found that only H3K14Ac is important and multiple BDs increase affinity. In cells, only H3K14Ac is present at the PBAF-bound inducible promoters! (8/11)

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Dykhuizen Lab @dykhuizenlab.bsky.social · 12/08/2026

With TGFB1, however, it was different. PBAF goes to numerous repressed genes, where it increases promoter accessibility and activates genes. So, maybe open active promoters don’t require PBAF accessibility, but closed ones need PBAF to start the process. But how does PBAF know where to go? (7/11)

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Dykhuizen Lab @dykhuizenlab.bsky.social · 12/08/2026

PBAF is highly enriched at promoters and is highly correlated with H3K4me3. Loss of PBRM1 reduced PBAF binding, but the promoters were still accessible and active, and there was no correlation to PBRM1-dependent gene expression. This is very different than cBAF's clear role at enhancers.(6/11)

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Dykhuizen Lab @dykhuizenlab.bsky.social · 12/08/2026

Alisha set out to understand this discrepancy. Using TGF-B1 in epithelial and cancer cells, she found that PBRM1 is indeed required for completion of EMT in vitro and metastsis in vivo. Using this inducible system, we also figured out a few interesting things about PBAF and gene regulation. (5/11)

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Dykhuizen Lab @dykhuizenlab.bsky.social · 12/08/2026

Luckily, the Wendt Lab was right next door with tons of expertise in breast cancer EMT and metastasis. Cool! We knocked down PBRM1 in a bunch of cell lines and models. His trainees were excited; loss of PBRM1 really worked well to decrease metastasis in all the models they tested! Wait, what? (4/11)

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Dykhuizen Lab @dykhuizenlab.bsky.social · 12/08/2026

Using RNA-Seq, we found that loss of PBRM1 in epithelial cells decreases cell adhesion genes, which comes up as epithelial-mesenchymal transition (EMT) in pathway analysis. So, we hypothesized that loss of PBRM1 increases metastasis, explaining its function as a tumor suppressor.(3/11)

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Dykhuizen Lab @dykhuizenlab.bsky.social · 12/08/2026

In 2013, sequencing revealed that PBRM1, a subunit of PBAF, is mutated in renal carcinoma. I always loved PBRM1 because it has six tandem bromodomains and I figured they must be important for some sort of unique and multivalent chromatin targeting. (2/11)

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Dykhuizen Lab @dykhuizenlab.bsky.social · 12/08/2026

Our PBAF paper is finally out in Science Advances! We’ve been working on this project for upwards of 10 years (depending on who you ask), with Alisha heading the effort (and doing most of the work) to understand the role of PBRM1 in breast cancer metastasis. www.science.org/doi/full/10..... (1/11)

science.org

PBRM1-dependent PBAF targeting is required for EMT and metastasis in breast cancer

During EMT, PBRM1 targets PBAF to H3K14Ac sites, opening chromatin to activate TGFβ targets and enable breast cancer metastasis.

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Reposted by Dykhuizen Lab

H. Courtney Hodges @hodgeshc.bsky.social · 22/07/2025

How do chromatin remodelers use #IDRs to find TF binding partners? In our new Molecular Cell paper, we show that β-catenin is an adaptor that links SWI/SNF (cBAF) subunit ARID1A with binding partners via IDR-domain interactions. www.cell.com/molecular-ce...

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Reposted by Dykhuizen Lab

Jordan Meier @doc-jlmeier.bsky.social · 10/04/2025

Great news: NIH postbac program is recruiting again! If your grad school plans were affected by program cutbacks or admissions freezes this year I highly encourage you to apply, this could be a perfect opportunity. Please repost. www.training.nih.gov/research-tra...

training.nih.gov

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Dykhuizen Lab @dykhuizenlab.bsky.social · 09/12/2024

No one told me about this before we went on our first cruise! 5 days of Frasier-esque shenanigans and miscommunications. Money well spent.

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