Darko Barisic

Darko Barisic

@darkobar.bsky.social

Assistant Professor of Cancer Biology at Weill Cornell Medicine — Chromatin & Epigenetics in Cancer and Immunity. https://barisiclab.weill.cornell.edu/

642 followers265 following68 posts

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Darko Barisic
@darkobar.bsky.social

Beyond thrilled that the first paper from our lab is out today in @nature.com! We show that SWI/SNF loss results in gain-of-function for CTCF and cohesin, reshaping the 3D genome, and an unexpected switch between chromatin remodeling complexes. Full thread below. www.nature.com/articles/s41...

nature.comSWI/SNF complexes shape 3D chromatin architecture through CTCF and cohesin - NatureLoss of function of canonical BAF induces gain of CTCF and cohesin binding that alters 3D genome architecture and reprograms transcription.
Darko Barisic
@darkobar.bsky.social

Beyond thrilled that the first paper from our lab is out today in @nature.com! We show that SWI/SNF loss results in gain-of-function for CTCF and cohesin, reshaping the 3D genome, and an unexpected switch between chromatin remodeling complexes. Full thread below. www.nature.com/articles/s41...

nature.comSWI/SNF complexes shape 3D chromatin architecture through CTCF and cohesin - NatureLoss of function of canonical BAF induces gain of CTCF and cohesin binding that alters 3D genome architecture and reprograms transcription.
View full thread
Darko Barisic
@darkobar.bsky.social

Beyond thrilled that the first paper from our lab is out today in @nature.com! We show that SWI/SNF loss results in gain-of-function for CTCF and cohesin, reshaping the 3D genome, and an unexpected switch between chromatin remodeling complexes. Full thread below. www.nature.com/articles/s41...

nature.comSWI/SNF complexes shape 3D chromatin architecture through CTCF and cohesin - NatureLoss of function of canonical BAF induces gain of CTCF and cohesin binding that alters 3D genome architecture and reprograms transcription.
View full thread
Darko Barisic
@darkobar.bsky.social

In summary, SWI/SNF loss can drive a gain of function: cBAF loss enables CTCF/cohesin gain and a switch to PBAF, rewiring the 3D genome and promoting proliferation. This reveals how tumor suppressor loss can lead to a growth advantage for cancer cells. 13/n

Darko Barisic
@darkobar.bsky.social

This work is a tremendous effort led by Sonia Debek (our lab's first postdoc!), Cem Meydan and Chris Chin. Huge congrats and thank you to all other co-authors for their incredible help.

Darko Barisic
@darkobar.bsky.social

Beyond thrilled that the first paper from our lab is out today in @nature.com! We show that SWI/SNF loss results in gain-of-function for CTCF and cohesin, reshaping the 3D genome, and an unexpected switch between chromatin remodeling complexes. Full thread below. www.nature.com/articles/s41...

nature.comSWI/SNF complexes shape 3D chromatin architecture through CTCF and cohesin - NatureLoss of function of canonical BAF induces gain of CTCF and cohesin binding that alters 3D genome architecture and reprograms transcription.
View full thread
Darko Barisic
@darkobar.bsky.social

Do we see a parallel in patients? In pan-cancer analyses, patients with alterations in both ARID1A and CTCF have better overall survival than those with ARID1A alterations alone. Also, high CTCF expression is associated with worse survival. 11/n

Darko Barisic
@darkobar.bsky.social

Finally, Arid1a loss in mice expands the germinal center dark zone, home to highly proliferative B cells. Deleting one copy of either Ctcf or the PBAF subunit Pbrm1 rescues this phenotype. Two genetic rescues connect the complex switch to cell behavior and phenotype. 12/n

Darko Barisic
@darkobar.bsky.social

Beyond thrilled that the first paper from our lab is out today in @nature.com! We show that SWI/SNF loss results in gain-of-function for CTCF and cohesin, reshaping the 3D genome, and an unexpected switch between chromatin remodeling complexes. Full thread below. www.nature.com/articles/s41...

nature.comSWI/SNF complexes shape 3D chromatin architecture through CTCF and cohesin - NatureLoss of function of canonical BAF induces gain of CTCF and cohesin binding that alters 3D genome architecture and reprograms transcription.
View full thread
Darko Barisic
@darkobar.bsky.social

Why would cells benefit from CTCF and PBAF gain upon cBAF loss? Faster proliferation. CTCF over-expression alone reproduces the growth advantage of ARID1A loss. Deleting the PBAF subunit ARID2 removes that advantage in ARID1A-mutant cells. 9/n

Darko Barisic
@darkobar.bsky.social

This is also true in mice. Embryonic fibroblasts proliferate faster after Arid1a loss, and genetically deleting both Ctcf and Arid1a restores normal growth. Interestingly, in our mouse lymphoma model, CTCF-site opening appears before overt disease and persists in tumors. 10/n

Darko Barisic
@darkobar.bsky.social

Beyond thrilled that the first paper from our lab is out today in @nature.com! We show that SWI/SNF loss results in gain-of-function for CTCF and cohesin, reshaping the 3D genome, and an unexpected switch between chromatin remodeling complexes. Full thread below. www.nature.com/articles/s41...

nature.comSWI/SNF complexes shape 3D chromatin architecture through CTCF and cohesin - NatureLoss of function of canonical BAF induces gain of CTCF and cohesin binding that alters 3D genome architecture and reprograms transcription.
View full thread
Darko Barisic
@darkobar.bsky.social

Next we asked: What helps CTCF gain when cBAF is lost? Surprisingly, PBAF. CTCF interacts with this distinct SWI/SNF complex that is recruited to sites gaining CTCF. We confirmed this interaction in several cancer cell lines from different tissue-of-origin. 7/n

Darko Barisic
@darkobar.bsky.social

To test if cBAF and PBAF switch happens on chromatin, we examined their binding with ChIP. In both lymphoma and breast cancer cells, sites that lose ARID1A binding upon ARID1A deletion gain PBAF, showing the complex switch at the same genomic sites. 8/n

Darko Barisic
@darkobar.bsky.social

Beyond thrilled that the first paper from our lab is out today in @nature.com! We show that SWI/SNF loss results in gain-of-function for CTCF and cohesin, reshaping the 3D genome, and an unexpected switch between chromatin remodeling complexes. Full thread below. www.nature.com/articles/s41...

nature.comSWI/SNF complexes shape 3D chromatin architecture through CTCF and cohesin - NatureLoss of function of canonical BAF induces gain of CTCF and cohesin binding that alters 3D genome architecture and reprograms transcription.
View full thread
Darko Barisic
@darkobar.bsky.social

Is gain of CTCF a direct response? Acute ARID1A loss in embryonic stem cells or SWI/SNF inhibition in cancer cells opened CTCF sites in a few hours. ChIP showed increased CTCF and decreased ARID1A binding at the same sites, supporting direct antagonism on chromatin. 5/n

Darko Barisic
@darkobar.bsky.social

So what did that do to genome folding? A lot. Large TADs split into smaller domains. Boundaries were stronger. Long-range contacts decreased and short-range ones increased. Interestingly, gained CTCF sites picked up more promoter-enhancer contacts and those genes went up. 6/n

Darko Barisic
@darkobar.bsky.social

Beyond thrilled that the first paper from our lab is out today in @nature.com! We show that SWI/SNF loss results in gain-of-function for CTCF and cohesin, reshaping the 3D genome, and an unexpected switch between chromatin remodeling complexes. Full thread below. www.nature.com/articles/s41...

nature.comSWI/SNF complexes shape 3D chromatin architecture through CTCF and cohesin - NatureLoss of function of canonical BAF induces gain of CTCF and cohesin binding that alters 3D genome architecture and reprograms transcription.
View full thread
Darko Barisic
@darkobar.bsky.social

We tested SWI/SNF loss across 15 human cell lines spanning 10 tissues, mouse tumor lines, primary mouse cells & Drosophila cells. We used SWI/SNF inhibitors or genetic deletions to ask whether a shared chromatin response emerges across tissues and species. 3/n

Darko Barisic
@darkobar.bsky.social

Across tissues and species, we found a shared response: chromatin opens at CTCF motifs upon SWI/SNF loss. ARID1A (cBAF) loss alone is sufficient. 4/n

Darko Barisic
@darkobar.bsky.social

Beyond thrilled that the first paper from our lab is out today in @nature.com! We show that SWI/SNF loss results in gain-of-function for CTCF and cohesin, reshaping the 3D genome, and an unexpected switch between chromatin remodeling complexes. Full thread below. www.nature.com/articles/s41...

nature.comSWI/SNF complexes shape 3D chromatin architecture through CTCF and cohesin - NatureLoss of function of canonical BAF induces gain of CTCF and cohesin binding that alters 3D genome architecture and reprograms transcription.
Darko Barisic
@darkobar.bsky.social

SWI/SNF complex mutations hit roughly 20% of patients across nearly every tumor type, yet a shared mechanism linking their loss to cancer remains unclear. When we started the lab 2.5 years ago, that was our first question: is there something in common across tissues? 2/n

Darko Barisic
@darkobar.bsky.social

🧬 💻 We're looking for a motivated postdoctoral associate in computational biology to join Barisic Lab at Weill Cornell Medicine and study chromatin remodeling and 3D genome organization. Please share and apply below: postdocs.weill.cornell.edu/opportunitie...

postdocs.weill.cornell.eduPostdoctoral Associate in Computational Biology | Office of Postdoctoral AffairsAs a Postdoctoral Associate in the Barisic Lab at Weill Cornell Medicine, you will work on projects focused on how chromatin remodeling complexes and 3D genome organization regulate cell differentiati...
Darko Barisic
@darkobar.bsky.social

Huge congratulations to my postdoc Jiali Yu 👏 who has been awarded a fellowship from the National Cancer Center. She’ll be investigating how chromatin remodelers contribute to the onset and progression of blood cancers. So proud and excited for what’s ahead. 🚀

Darko Barisic
@darkobar.bsky.social

Huge congrats to *Ari Melnick* on being appointed the Director of the Josep Carreras Leukemia Research Institute in Barcelona! 🙌 👏

Josep Carreras Leukaemia Research Institute@carrerasijc.bsky.social

We're pleased to announce that Dr Ari Melnick has been appointed new Director of the Josep Carreras Institute. Dr Melnick will lead IJC in our mission to advance #research in #leukaemia and other malignant blood diseases. Read the full release here: www.carrerasresearch.org/en/news/dr-a...

Darko Barisic reposted

Elena Grossi
@elenagr.bsky.social

🎉 Excited to share my postdoc work in the Bernstein lab now online @cp-molcell.bsky.social! 🔎We explored the unique functions of the SWI/SNF PBAF complex and its relationship with TFs, and unveiled a PBAF/REST-controlled neuronal-like signature with potential implications in #melanoma brain mets🧬

cell.comThe SWI/SNF PBAF complex facilitates REST occupancy at repressive chromatinBy mapping SWI/SNF complex subfamilies in the melanocytic lineage, Grossi and Nguyen et al. find that PBAF-only sites harbor PRC1/2 modifications and the repressive transcription factor REST. PBAF is ...
Darko Barisic
@darkobar.bsky.social

Absolutely fantastic work from the magnificent @davidlabmsk.bsky.social lab! Incredible science and amazing out-of-the-box approach. Congrats to all the authors and highly recommend the read. 🙌

Yael David@yaeldavidmsk.bsky.social

I am extremely proud to see our work about Hepatitis B now published in @cellpress.bsky.social From basic research to identifying the key step of infection & a potential first drug for curing this devastating disease. This has been an incredible journey.🧵 www.cell.com/cell/fulltex...

cell.comA nucleosome switch primes hepatitis B virus infectionA reconstituted cccDNA platform facilitated the discovery of an early chromatinization event that promotes transcription of the hepatitis B virus (HBV) regulatory X gene. The use of a small-molecule c...
Darko Barisic
@darkobar.bsky.social

Impressed by Genome-Shuffle-seq. 🔀 “Multiplex generation and single-cell analysis of structural variants in mammalian genomes”. www.science.org/doi/10.1126/...

science.orgMultiplex generation and single-cell analysis of structural variants in mammalian genomesStudying the functional consequences of structural variants (SVs) in mammalian genomes is challenging because (i) SVs arise much less commonly than single-nucleotide variants or small indels and (ii) ...
Darko Barisic
@darkobar.bsky.social

Long-read sequencing just got an upgrade. 📢 Genome, methylome, epigenome & transcriptome in one go—haplotype-resolved & at single-molecule resolution. 🔥

Eric Topol@erictopol.bsky.social

The "kitchen sink" of omics to solve the basis for an undiagnosed disease: long read genome , transcriptome, methytome, epigenome, all synchronized (a first) www.nature.com/articles/s41...

nature.comSynchronized long-read genome, methylome, epigenome and transcriptome profiling resolve a Mendelian condition - Nature GeneticsSimultaneous profiling of the genome, methylome, epigenome and transcriptome using single-molecule chromatin fiber sequencing and multiplexed arrays isoform sequencing identifies the genetic and molec...
Darko Barisic
@darkobar.bsky.social

PRINT is finally out. 🖨️ Highly recommend this paper! Congrats to Buenrostro group and all the authors. 🙌 “Multiscale footprints reveal the organization of cis-regulatory elements.” www.nature.com/articles/s41...

nature.comMultiscale footprints reveal the organization of cis-regulatory elements - NatureWe developed PRINT, a computational method that identifies footprints of DNA–protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.

Darko Barisic reposted

ivanraimondi.bsky.social
@ivanraimondi.bsky.social

🧬 We’re excited to introduce D&D-seq, a single-cell technology that maps DNA:Protein interactions through molecular footprinting. Check it out here: biorxiv.org/content/10.1... #Genomics #Epigenetics

biorxiv.orgSingle-cell mapping of regulatory DNA:Protein interactionsGene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibil...
Darko Barisic
@darkobar.bsky.social

Huge congrats to Béguelin lab at Weill Cornell. Fantastic new work showing how PRC2 inhibition boosts T cell immunotherapies. Out now in Cancer Cell. www.cell.com/cancer-cell/...

cell.comEZH2 inhibition enhances T cell immunotherapies by inducing lymphoma immunogenicity and improving T cell functionIsshiki et al. demonstrate that EZH2 inhibitors re-activate immune synapse functions between B cell lymphomas and T cells, sensitizing lymphomas to T cell immunotherapies. EZH2 inhibition enhances killing activity by promoting T cell recruitment, prolonging binding and increasing contact surface with lymphoma cells, and prevents T cell exhaustion. This strategy is currently under clinical evaluation.

Darko Barisic reposted

Marcelo Bonini, Ph.D.
@mbonini.bsky.social

H3-H4 histone dimers act as copper reductase. This is important because ETC and SOD1 require bio-usable Cu+ for function. This article shows a new mechanism by which chromatin histones can affect the cell metabolism via a new role in metal processing #redoxepigenetics www.science.org/doi/10.1126/...

science.orgThe histone H3-H4 tetramer is a copper reductase enzymeA eukaryotic histone complex can package DNA but is also a cupric reductase that provides biousable Cu1+ for the cell.

Darko Barisic reposted

Lluis Morey
@lluismorey.bsky.social

Very interesting paper from @mitchguttman.bsky.social previously in @biorxivpreprint.bsky.social out in Nature Genetics. "ChIP-DIP generates context-specific protein localization maps at consortium scale" www.nature.com/articles/s41...

nature.comChIP-DIP maps binding of hundreds of proteins to DNA simultaneously and identifies diverse gene regulatory elements - Nature GeneticsChIP-DIP (ChIP done in parallel) is a highly multiplex assay for protein–DNA binding, scalable to hundreds of proteins including modified histones, chromatin regulators and transcription factors, offe...

Darko Barisic reposted

Anshul Kundaje
@anshulkundaje.bsky.social

www.nature.com/articles/s41... Single-molecule states link transcription factor binding to gene expression Deep insights into multiple facets of TF binding, accessibility & expression with biophysical models of single molecule data by Ben Doughty, Michaela Hinks, Bintu & Greenleaf labs

nature.comSingle-molecule states link transcription factor binding to gene expression - NatureA study uses single-molecule footprinting to measure protein occupancy at regulatory elements on individual molecules in human cells and describes how different properties of transcription factor bind...
Darko Barisic
@darkobar.bsky.social

cBAF generates subnucleosomes that expand OCT4 binding and function beyond DNA motifs at enhancers. www.nature.com/articles/s41...

nature.comcBAF generates subnucleosomes that expand OCT4 binding and function beyond DNA motifs at enhancers - Nature Structural & Molecular BiologyHere, the authors show that the canonical BRG/BRM-associated factor (SWI/SNF) chromatin remodeler generates subnucleosomes containing 50–80 bp of DNA associated with the four core histones. These hemi...

Darko Barisic reposted

Lluis Morey
@lluismorey.bsky.social

Beautiful and fundamental paper about Polycomb-mediated gene repression by @kjarmache.bsky.social Read–write mechanisms of H2A ubiquitination by Polycomb repressive complex 1 www.nature.com/articles/s41...

nature.comRead–write mechanisms of H2A ubiquitination by Polycomb repressive complex 1 - NatureCryo-electron microscopy and biochemical studies elucidate the read–write mechanisms of non-canonical PRC1-containing RYBP in histone H2A lysine 119 monoubiquitination and their roles in maintaining e...

Darko Barisic reposted

Vijay Ramani
@vram142.bsky.social

The latest from our group, led by Megan Ostrowski and @martyyang.bsky.social, is now published in final form (www.cell.com/cell/fulltex...! Many thanks to our excellent peer reviewers for suggesting several experiments (including CAF-1 perturbation) to really improve the study =) #epigenetics

cell.comThe single-molecule accessibility landscape of newly replicated mammalian chromatinBy developing a long-read sequencing method to simultaneously map replication status and protein-DNA contacts in cells, Ostrowski, Yang, et al. show that newly replicated chromatin is enriched for unw...