Sarah Hainer

Incredibly proud to share our new preprint, lead by the Incomparable Rithika Sankar. Here we temporally dissect the role of FACT in mES cells, finding that FACT loss drives progressive deterioration of chromatin architecture, leading to transcriptional collapse. www.biorxiv.org/content/10.6...

@caitlyncardetti.bsky.social

25 Aug

Precisely 20 years after Takahashi and Yamanaka reported fibroblast reprogramming with OSKM to iPSCs, we are excited to invite articles to our BMC Biology collection. Please see our short editorial here: link.springer.com/article/10.1... And submit your amazing work to this celebratory collection!

Sarah Hainer reposted

Caitlyn Cardetti, PhD

10 Aug

📢 Call for papers - Pluripotency, differentiation, and reprogramming 📢 #BMCBiology Guest Editors: Sekyu Choi, Pohang Ge Guo, Exeter @hainerlab.bsky.social Masaki Kinoshita, Nottingham @stanleystrawbridge.bsky.social Chengchen Zha, Westlake Fan Zhou, Tsinghua link.springer.com/collections/...

link.springer.comPluripotency, differentiation, and reprogrammingBMC Biology invites submissions to our Collection on Pluripotency, differentiation, and reprogramming. This Collection highlights the molecular and cellular ...

17 July

Hi friends! I am a guest editor for a new collection in BMC Biology called "Pluripotency, differentiation, and reprogramming" and we just opened for submissions. Looking for research articles and reviews, please reach out if you are interested. I'm excited for helping with this collection!

dx.doi.orgMolecular Acrobats: How CHD Remodelers Shape the Genetic Playground to License Cell IdentityIn eukaryotes, DNA is not a naked repository of genetic information but is tightly wound around histone octamers to form nucleosomes. While this packaging solves the spatial problem of fitting 2 mete...

13 July

The talented @isa-ozdemir.bsky.social wrote a review of CHD remodelers, discussing all 9 family members and their roles in ES cells and early development. dx.doi.org/10.1002/bies... 1/2

Genetics Society of America

13 July

Included is discussion of domains, localization and function. I especially love the molecular acrobat metaphor he created to make this accessible! 2/2

Sarah Hainer reposted

PLOS Biology

@plosbiology.org

16 June

How has #evolution shaped Transcription Elongation Factors, important for #GeneExpression? This study by Alex Francette, Karen Arndt &co traces ten core factors to the last eukaryotic common ancestor, and shows they display both conserved and lineage-specific domains. 🧪#AcademicSky plos.io/4eaCUTJ

Sarah Hainer reposted

@genetics-gsa.bsky.social

27 Apr

New in #GENETICS from @hainerlab.bsky.social: The nucleosome remodelers esBAF and INO80 selectively influence subcompartment identity and enhancer–promoter communication at key regulatory loci during higher-order chromatin organization in mice. 🔗 buff.ly/0eU5xg0

Sarah Hainer reposted

Mark Peifer (He, him)

@peiferlabunc.bsky.social

2 May

Great thread from an @nationalacademies.org award winner highlighting the current cowardice and capitulation of NAS, tech industry and the leaders of both to the demands of Trump that are destroying American science 🧪

M.J. Crockett@mjcrockett.bsky.social

Last weekend I received the Troland Research Award from the @nationalacademies.org. I’m so grateful to the communities who made this work possible. It's strange to receive this award at a time when much of the work being recognized is not eligible for federal funding. My remarks 👇 and a 🧵>>

youtube.comNAS 163rd Annual Meeting - Awards CeremonyYouTube video by National Academy of Sciences

Sarah Hainer reposted

Craig Kaplan

@triggerloop.bsky.social

Three @biorxivpreprint.bsky.social preprints on acute depletion of FACT in ES cells. First, from my colleague at Pitt Sarah Hainer's lab 1/ www.biorxiv.org/content/10.6...

We are grateful to the Milne group for discussion of their data prior to posting and submission and encourage you to look at their beautiful work www.biorxiv.org/content/10.6...

Please send us feedback! Also, Rithika is beyond amazing and please watch for her applications in the near future :)

We are grateful to @epicypher.bsky.social for sharing the Hia5 enzyme and assisting with Fiber-seq.

We are grateful to the @dewitlab.bsky.social lab for sharing the SOX2-dTAG and NANOG-dTAG cell lines that served as nice controls (see Supp Fig. 3!)

Together these data reveal a temporal cascade in which FACT depletion causes 5’ loss of nucleosomes and their associated histone modifications. This chromatin disruption occurs prior to transcriptional inhibition More in the paper so take a look!

We are grateful to @flurylab.bsky.social and @groth-anja.bsky.social for sharing their SSRP1-dTAG cell line with us, and encourage you to take a peek at their amazing manuscript also online: www.biorxiv.org/content/10.6...

So what impact does this have? Well, loss of histone recycling leads to a build up of RNAPII in the 5' end of genes and reduced transcription elongation, as indicated by changes to H3K36me3.

Ultimately, we observe transcriptional collapse and more specifically downregulation of genes. But this happens well after the initial reduction in nucleosome phasing observed.

This suggests that FACT loss is leading to a partially irreversible alteration to the epigenome.

I told you that FACT's impact is greatest at highly transcribed locations, but does it require transcription? Again inspired by the Robert lab, we show that yes, FACT's function is dependent on transcription

Is the 5' nucleosome loss and increased TF invasion occurring at the same place? Yes! Over highly transcribed locations especially, which rely more on FACT activity

Can we rescue this defect by bringing FACT back? Work led by our amazing undergraduate research Bryona Jackson found that there is only a partial restoration. Note for others: washing out dTAG doesn't always work, so we resorted to crafty ways of rescuing. But not full restoration.

How is this happening? Beautiful work from F. Robert group in budding yeast found FACT is important for recycling of histone PTMs, and inspired by this we hypothesized that chromatin opening would permit TF invasion. We found that 5' nucleosome phasing is lost over time in FACT depletion.

We corroborated our short read sequencing results with single molecule long read Fiber-seq and found reduce 5' and increased 3' nucleosomes in FACT depletion

Following up from our prior study that examined FACT function in ES cells (link.springer.com/article/10.1...) we asked whether FACT regulates transcription factor occupancy. Given that FACT loss leads to differentiation, our simple model was that FACT depletion would result in reduced TF occupancy.

@denisduboule.bsky.social

However, using rapid dTAG depletion and high resolution time course analysis, we find that FACT depletion results in TF impingement into gene bodies, in a sequence independent manner, but occurring more readily over highly transcribed genes.

Sarah Hainer reposted

Denis Duboule

15 Feb

Very sad news. Gail Martin (1944-2026) was a figure in developmental biology. She pioneered the field of ES cells. A great colleague, a friend and a lovely person.

Sarah Hainer reposted

Crystal D. Rogers

@rogerslabucd.bsky.social

6 Feb

Happy Black History Month! I am sharing a permanent and continuously updated list of inspiring Black scientists! Check it out! Huge thank you to the folks who gathered this info. Thank you to @drstarbird.bsky.social and the rest of the Index Committee! www.wiley.com/en-us/resear...

wiley.comIndex of Inspiring Black Scientists | WileyThe Inspiring Black Scientists Index is a curated database celebrating diverse contributions to science. Join us in promoting education and collaboration.

cbc.caRead Mark Carney's full speech on middle powers navigating a rapidly changing world | CBC NewsRead the full text of Prime Minister Mark Carney's speech about a shakeup of the global order and role of middle powers at the World Economic Forum in Davos, Switzerland.

21 Jan

Proud to be Canadian 🇨🇦 www.cbc.ca/news/politic...

Sarah Hainer reposted

Prasad Jallepalli, MD, PhD

@prasad.bsky.social

14 Dec 2025

* vaccines keep kids from dying * guns cause kids to die these are unassailable conclusions based on mountains of evidence it is a crying shame that politicians pretend otherwise, endangering our kids and everyone else’s

biorxiv.orgesBAF and INO80C fine-tune subcompartments and differentially regulate enhancer-promoter interactionsThe genome is compacted in the nucleus through a hierarchical chromatin organization, ranging from chromosome territories to compartments, topologically associating domains (TADs), and individual nucl...

New preprint is up, led by former postdoc Braulio Bonilla. We know these remodelers regulate nucleosome positions and occupancy, but do they have a role in regulating higher order chromatin structure? We take a peek for BAF and INO80C. www.biorxiv.org/content/10.1...

Overall, our study suggests that esBAF and INO80 have limited influence on large-scale 3D genome architecture. However, subcompartment organization is sensitive to remodeler depletion, indicating a more nuanced role for these complexes in shaping chromatin topology at sub-megabase scales.

And while there were also minimal impacts on loops, our PCMC data suggest that BAF and INO80C are not general regulators of chromatin looping but may instead fine-tune regulatory interactions at distinct key developmental loci in ES cells.

Therefore, to investigate the impact of these remodelers more directly on enhancer-promoter loops, we performed promoter capture microC (PCMC) and found that KD of BAF ATPase BRG1 results in decreases in some E-P loops and KD of INO80C ATPase Ino80 results in increases in some E-P loops.

For both these remodelers, these tend to be OSN bound and also Suz12 bound, and enriched as bivalent promoters. Together, these data suggest that the enhancer-promoter loops esBAF promotes and INO80C restricts are pluripotency and bivalency related.

Similar to work from the Schubeler lab for BAF, we find that loss of neither BAF nor INO80C impact TAD structures significantly.

Although we sequenced our Hi-C datasets deeply, we had a tough time calling non-architectural loops (most loops were CTCF-based, and not as many were TSS-based)

However, there is a reproducible effect on subcompartment structures, where upon KD of either ATPase, we observed a modest increase in the total amount of the genome assigned to inactive subcompartments, especially at locations that these remodelers bind and regulate transcription.

We therefore thing that BRG1 and INO80 contribute to the maintenance of active subcompartment organization (we are saying "fine-tune"), with effects that are especially pronounced at loci where these remodelers bind and/or their loss impacts transcription.