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Sarah Hainer

@hainerlab.bsky.social
932 followers 353 following 76 posts

Associate Prof @PittBioSci studying transcription dynamics and chromatin biology | passionate about equity in STEM | she/her

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Sarah Hainer @hainerlab.bsky.social · 25/08/2026
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!
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Caitlyn Cardetti, PhD @caitlyncardetti.bsky.social · 10/08/2026
📢 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.com
Pluripotency, differentiation, and reprogramming
BMC Biology invites submissions to our Collection on Pluripotency, differentiation, and reprogramming. This Collection highlights the molecular and cellular ...
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Sarah Hainer @hainerlab.bsky.social · 17/07/2026
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!
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Sarah Hainer @hainerlab.bsky.social · 13/07/2026
Included is discussion of domains, localization and function. I especially love the molecular acrobat metaphor he created to make this accessible! 2/2
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Sarah Hainer @hainerlab.bsky.social · 13/07/2026
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
dx.doi.org
Molecular Acrobats: How CHD Remodelers Shape the Genetic Playground to License Cell Identity
In 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...
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PLOS Biology @plosbiology.org · 16/06/2026
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
The authors' proposed model reflecting the acquisition and putative loss of transcription elongation factor domains across clades in the Tree of Life
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Genetics Society of America @genetics-gsa.bsky.social · 27/04/2026
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
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Mark Peifer (He, him) @peiferlabunc.bsky.social · 02/05/2026
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 🧪
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Craig Kaplan @triggerloop.bsky.social · 27/02/2026
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...
biorxiv.org
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
Please send us feedback! Also, Rithika is beyond amazing and please watch for her applications in the near future :)
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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...
biorxiv.org
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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!)
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
We are grateful to @epicypher.bsky.social for sharing the Hia5 enzyme and assisting with Fiber-seq.
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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...
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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!
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
Ultimately, we observe transcriptional collapse and more specifically downregulation of genes. But this happens well after the initial reduction in nucleosome phasing observed.
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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.
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
This suggests that FACT loss is leading to a partially irreversible alteration to the epigenome.
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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.
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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.
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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.
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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.
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Sarah Hainer @hainerlab.bsky.social · 27/02/2026
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...
biorxiv.org
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Denis Duboule @denisduboule.bsky.social · 15/02/2026
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.
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Crystal Rogers, PhD @rogerslabucd.bsky.social · 06/02/2026
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.com
Index of Inspiring Black Scientists | Wiley
The Inspiring Black Scientists Index is a curated database celebrating diverse contributions to science. Join us in promoting education and collaboration.
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Sarah Hainer @hainerlab.bsky.social · 21/01/2026
Proud to be Canadian 🇨🇦 www.cbc.ca/news/politic...
cbc.ca
Read Mark Carney's full speech on middle powers navigating a rapidly changing world | CBC News
Read 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.
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Prasad Jallepalli, MD, PhD @prasad.bsky.social · 14/12/2025
* 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
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Dr. Kat Napaaqtuk❄️ @napaaqtuk.bsky.social · 27/09/2025
Comment period ends on Monday for a proposed rule change that would terminate student visas after 4 years. It also puts limits on exchange visitors and reps of foreign media, and shortens the length of time at the end of the visa from 60 days to 30 days. www.federalregister.gov/documents/20...
federalregister.gov
Establishing a Fixed Time Period of Admission and an Extension of Stay Procedure for Nonimmigrant Academic Students, Exchange Visitors, and Representatives of Foreign Information Media
Unlike most nonimmigrant classifications, which are admitted for a fixed time period, aliens in the F (academic student), J (exchange visitor), and most I (representatives of foreign information media...
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Sarah Hainer @hainerlab.bsky.social · 18/09/2025
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.
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Sarah Hainer @hainerlab.bsky.social · 18/09/2025
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.
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Sarah Hainer @hainerlab.bsky.social · 18/09/2025
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.
Enhancer-promoter loops impacted by BRG1 or INO80 loss are enriched for OCT4, SOX2, NANOG and SUZ12, and are described as bivalent locations.
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Sarah Hainer @hainerlab.bsky.social · 18/09/2025
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.
Promoter capture microC (PCMC) enriches for TSS-based loops and shows decreased loops in Brg1 KD and increased loops in Ino80 KD
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Sarah Hainer @hainerlab.bsky.social · 18/09/2025
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)
Our Hi-C data detects limited TSS-based loops, but is enriched for CTCF-based (architectural) loops
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Sarah Hainer @hainerlab.bsky.social · 18/09/2025
Similar to work from the Schubeler lab for BAF, we find that loss of neither BAF nor INO80C impact TAD structures significantly.
Hi-C data analyzed for TAD structures
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Sarah Hainer @hainerlab.bsky.social · 18/09/2025
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.
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Sarah Hainer @hainerlab.bsky.social · 18/09/2025
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.
subcompartment analysis of Hi-C data showing impact of remodeler depletion on subcompartments
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Sarah Hainer @hainerlab.bsky.social · 18/09/2025
48hr KD of the ATPase subunit for either complex has almost not impact on compartments, assessed by Hi-C:
heatmaps from Hi-C data showing compartment structures
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Sarah Hainer @hainerlab.bsky.social · 18/09/2025
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...
biorxiv.org
esBAF and INO80C fine-tune subcompartments and differentially regulate enhancer-promoter interactions
The genome is compacted in the nucleus through a hierarchical chromatin organization, ranging from chromosome territories to compartments, topologically associating domains (TADs), and individual nucl...
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Sarah Hainer @hainerlab.bsky.social · 29/08/2025
Oh please add me! Thank you for making this!
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Lucas Farnung @lucas.farnunglab.com · 29/08/2025
🧬 Transcription elongation by RNA polymerase II relies on a web of elongation factors. Our new work shows how IWS1 acts as a modular scaffold to stabilize & stimulate elongation. Fantastic work by Della Syau! www.biorxiv.org/content/10.1...
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Sarah Hainer @hainerlab.bsky.social · 29/08/2025
These studies describe a mechanism by which the Chd1 is coupled to transcription elongation and the molecular consequences when this coupling is disrupted and provide insight into a domain in Chd1 for which little is known.
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Sarah Hainer @hainerlab.bsky.social · 29/08/2025
the Rtf1 mutation not being sufficient to break the interaction, and/or represent the complexity and redundancy present in this more complicated system.
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Sarah Hainer @hainerlab.bsky.social · 29/08/2025
So in a murine cell line system (ES cells) what happens? We made the CHCT deletions and an Rtf1 mutation ES cell line, but did not observe the same nucleosome shifts. This may be due to reduced protein levels observed in the Chd1 and Chd2 CHCT deletion cell lines...
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Sarah Hainer @hainerlab.bsky.social · 29/08/2025
Chd1 and Rtf1 are conserved proteins, so we wanted to know if this interaction is conserved in mammalian systems. Y2H using murine constructs demonstrate an interaction between Chd1 and Rtf1 as well as the related remodeler, Chd2, and Rtf1. CHCT deletions and Rtf1 mutations reduce this interaction
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Sarah Hainer @hainerlab.bsky.social · 29/08/2025
Histone PTMs, K4me3 and K36me3 are also shifted 5'
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Sarah Hainer @hainerlab.bsky.social · 29/08/2025
Notably, these precise interaction mutants seem to have a greater defect in nucleosome localization relative to full deletion, which demonstrates the multifunctional aspect of these proteins as well as the need for precision mutations.
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Sarah Hainer @hainerlab.bsky.social · 29/08/2025
As Chd1 is an important nucleosome remodeler, what does this loss of appropriate localization mean to genic nucleosomes? Well, nucleosomes (and overlapping dinucleosomes aka hexasome-nucleosomes) are also shifted 5', and this is exacerbated in Isw1 delete.
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