@BintuLab

Single-cell chromatin and gene regulation dynamics for better cell engineering @ Stanford BioE

 Stanford, CA
bintulab.com/
Joined November 2018
  • Tweets105
  • Following156
  • Followers1.5K
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Numerous biotech innovations started with adapting a protein to its non-native context, which often requires substantial experimental optimizations. Here’s a breakdown by our lead, @Xiaowei0402, on a versatile, efficient computational framework to facilitate such adaptations.
Xiaowei Zhang@Xiaowei0402Oct 20
We deimmunized a clinical CD19 CAR binder with experimentally detected HLA-I epitope depletion while retaining tumor killing, and rescued a secreted protease to function in the cytosol. Both done with one unified design framework: ProVADA. How it works and what we tested 🧵 (1/11)
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Jesse Engreitz@jengreitzOct 9
Check out Swap-seq — our next-gen tech for tiled twin prime deletion mapping of distal regulatory elements biorxiv.org/content/10.6... Please get in touch if you’d like to try it out! Thread 👇
Xiangmeng(Shawn) Cai@XiangmengCaiOct 9
Have you ever looked at a gene in IGV or a genome browser and wondered “What are all those (ATAC-seq/H3K27ac/CTCF ChIP-seq/…) peaks doing?” 🤔 I’m thrilled to share that we developed a new technology called Swap-seq to answer that exact question. biorxiv.org/content/10.64898…

Systematic mapping of enhancers, silencers, and topological elements with prime editing deletion...

Noncoding regulatory elements in the human genome can control gene expression through distinct mechanisms, including acting as enhancers, silencers, or topological elements. However, we lack tools to...

biorxiv.org
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Have you ever looked at a gene in IGV or a genome browser and wondered “What are all those (ATAC-seq/H3K27ac/CTCF ChIP-seq/…) peaks doing?” 🤔 I’m thrilled to share that we developed a new technology called Swap-seq to answer that exact question. biorxiv.org/content/10.64898…

Systematic mapping of enhancers, silencers, and topological elements with prime editing deletion...

Noncoding regulatory elements in the human genome can control gene expression through distinct mechanisms, including acting as enhancers, silencers, or topological elements. However, we lack tools to...

biorxiv.org
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Eli Costa@ECosta173Sep 12
Excited to share some recent collaborative work between the Bintu and Ferrell labs investigating single-cell and population-level transcriptional response functions in minimal mammalian expression systems! biorxiv.org/content/10.64898…

Stable epigenetic states set single-cell activation thresholds in mammalian expression systems

Quantitatively relating transcription factor (TF) input to gene expression output is central to understanding mammalian gene regulation and essential for designing predictable synthetic expression...

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We used HT-recruit repeatedly to discover new protein domains involved in gene regulation and test many mutants. It can be used for domains associated with other functions (if you have a reporter). Now we published a detailed protocol on how to do it: nature.com/articles/s41596-0…

High-throughput measurements of protein domain functions using magnetic separation

Nature Protocols - This Protocol presents a scalable magnetic separation-based method for screening large protein domain libraries in mammalian cells, providing a simple and quantitative...

nature.com
Josh Tycko@JoshTyckoJun 30
We hope this protocol is useful for people doing large scale protein function work! nature.com/articles/s41596-0… Led by @abbythurm from @BintuLab

High-throughput measurements of protein domain functions using magnetic separation

Nature Protocols - This Protocol presents a scalable magnetic separation-based method for screening large protein domain libraries in mammalian cells, providing a simple and quantitative...

nature.com
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So we beat on. Gene/cell therapies often use proteins that could be recognized/rejected as non-self by our immune system. We combine algorithms to build proteins that are therapeutically relevant and can masquerade as our own parts doi.org/10.1101/2025.02.24.6…
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Incredibly excited that our paper linking single molecule states of TF binding to gene expression using quantitative thermodynamic models is out in Nature today. An amazing collaboration with the Bintu Lab. Congrats to Ben, Michaela, and Julia! nature.com/articles/s41586-0…

Single-molecule states link transcription factor binding to gene expression

Nature - A 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...

nature.com
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Development of compact transcriptional effectors using high-throughput measurements in diverse contexts go.nature.com/3NMu00N
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Lastly, I would also like to give a shout out to Nate Hathaway’s lab @UNCPharmacy for writing a beautiful preview article elegantly describing our work. Please check it out here! : shorturl.at/hycOp (4/4)
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I'm thrilled to announce that my PhD thesis work from @BintuLab on how the H3.3K36M oncohistone disrupts the establishment of epigenetic memory is now out in the latest issue of @MolecularCell. shorturl.at/X9IZG (1/4)
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Online Now: The H3.3K36M oncohistone disrupts the establishment of epigenetic memory through loss of DNA methylation dlvr.it/TF93Ry
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Join us in Heidelberg for this great conference! Submit an abstract, we will select 20 talks (you have to register in the system first: embl.ungerboeck.com/PROD/emc… )
EMBL Events
@EMBLEvents20 Aug 2024
🧬🙌🏻 Only a week left to submit your abstract for 'Quantitative biology to molecular mechanisms' – over 20 talks will be selected from abstracts, with a priority for early stage researchers, so don't miss your chance! #EMBLOmics ➡️ s.embl.org/omx24-01 📜 Deadline: 27 Aug
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🧬How do transcriptional cofactors recognize which genes to regulate?🧬 Check out our new preprint from @fordycelab @BintuLab that tackles this question and provides the first-ever quantitative map of disordered transcriptional protein interactions (1/9) biorxiv.org/content/10.1101/…

High-throughput affinity measurements of direct interactions between activation domains and...

Sequence-specific activation by transcription factors is essential for gene regulation[1][1],[2][2]. Key to this are activation domains, which often fall within disordered regions of transcription...

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(1/16) Check out our @SimonMJGaudin paper tiny.cc/icuazz from the Canzio lab out in @ScienceMagazine today on how tuning local cohesin trajectories enables differential readout of the clustered Protocadherin (Pcdh) locus across different types of neurons.
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Got out of the nucleus! Tested ~30,000 tiles from human RNA-binding proteins, found lots of domains that downregulate RNA&built an inducible synthetic RNA-binding protein for keeping target RNA at constant intermediate levels: biorxiv.org/content/10.1101/… So many follow-up projects!

High-throughput discovery of regulatory effector domains in human RNA-binding proteins

RNA regulation plays an integral role in tuning gene expression and is controlled by thousands of RNA-binding proteins (RBPs). We develop and use a high-throughput recruitment assay (HT-RNA-Recruit)...

biorxiv.org
Abby Thurm@abbythurm22 Jul 2024
Do human RNA-binding proteins have modular regulatory domains that downregulate RNA lifetimes? Our preprint @BintuLab studying this question is now out on bioRxiv, where we indeed identify small domains in RBPs that potently induce RNA degradation! biorxiv.org/content/10.1101/… (1/9)

High-throughput discovery of regulatory effector domains in human RNA-binding proteins

RNA regulation plays an integral role in tuning gene expression and is controlled by thousands of RNA-binding proteins (RBPs). We develop and use a high-throughput recruitment assay (HT-RNA-Recruit)...

biorxiv.org
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Our first RNA-centric preprint is online! Congratulations to @abbythurm and the whole team - we're so excited to continue learning about effector domains in RBPs, and to hear your thoughts about what could come next!
Abby Thurm@abbythurm22 Jul 2024
Do human RNA-binding proteins have modular regulatory domains that downregulate RNA lifetimes? Our preprint @BintuLab studying this question is now out on bioRxiv, where we indeed identify small domains in RBPs that potently induce RNA degradation! biorxiv.org/content/10.1101/… (1/9)

High-throughput discovery of regulatory effector domains in human RNA-binding proteins

RNA regulation plays an integral role in tuning gene expression and is controlled by thousands of RNA-binding proteins (RBPs). We develop and use a high-throughput recruitment assay (HT-RNA-Recruit)...

biorxiv.org
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We are hiring a lab manager/research assistant! More details and how to apply here: bintulab.com/2024/06/01/hiri…

Outdated: Hiring Lab Manager/Research Assistant

An opening is available for a job (1-2 year commitment, 2 years preferred) as lab manager and research assistant in the Bintu Lab in the Department of Bioengineering at Stanford University. The Bin…

bintulab.com
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A little late, but we're excited to share our preprint in collaboration with the Greenleaf lab that uses single-molecule footprinting at an engineered locus in mammalian cells to understand how TF occupancy dictates expression!
William J. Greenleaf@WJGreenleaf5 Feb 2024
Our work using single-molecule chromatin configurations to link TF binding to gene expression is now out on bioRxiv! Amazing effort from @bgrdoughty, @MichaelaThinks, and @juliaschaepe, and an immensely rewarding collaboration with the @BintuLab: biorxiv.org/content/10.1101/… [1/n]

Single-molecule chromatin configurations link transcription factor binding to expression in human...

The binding of multiple transcription factors (TFs) to genomic enhancers activates gene expression in mammalian cells. However, the molecular details that link enhancer sequence to TF binding,...

biorxiv.org
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Finally, I would like to note that the NFZ TAD developed by @JoshTycko, @BintuLab , and Bassik lab (link below) works very well in the synZiFTR toolkit, AND it can be further boosted with our new enhancement. That's all for now -- please stay tuned! 4/n biorxiv.org/content/10.1101/…

Development of compact transcriptional effectors using high-throughput measurements in diverse...

Human nuclear proteins contain >1000 transcriptional effector domains that can activate or repress transcription of target genes. We lack a systematic understanding of which effector domains regulate...

biorxiv.org
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It's a double feature on epigenetic memory today! Check another amazing new preprint on single-cell chromatin compaction and memory establishment from wizard postdoc @fjmrt!
Taihei Fujimori@fjmrt11 Oct 2023
New preprint! We studied how single-cell 3D chromatin structure changes under targeted epigenetic perturbations using multiplexed DNA FISH and synthetic biology tools, and found an intriguing relationship between chromatin compaction and epigenetic memory. biorxiv.org/content/10.1101/…

Single-cell chromatin state transitions during epigenetic memory formation

Repressive chromatin modifications are thought to compact chromatin to silence transcription. However, it is unclear how chromatin structure changes during silencing and epigenetic memory formation....

biorxiv.org
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