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Reposted by Mitch Guttman

Waggoner Lab @labwaggoner.bsky.social · 22/07/2025

SPIDR enables multiplexed mapping of RNA-protein interactions and uncovers a mechanism for selective translational suppression upon cell stress @cellcellpress.bsky.social @mitchguttman.bsky.social www.cell.com/cell/fulltex...

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Mitch Guttman @mitchguttman.bsky.social · 26/07/2025

This work was led by co-first authors Jimmy Guo and Erica Wolin with support from amazing teams from our lab @caltech.edu and the Jovanovic lab @columbiauniversity.bsky.social and @jbquerido.bsky.social lab with financial support from NHGRI, NSF, @genometdcc.bsky.social.

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Mitch Guttman @mitchguttman.bsky.social · 26/07/2025

We used SPIDR to identify mTOR-dependent changes and observed that 4EBP1 showed a dramatic increase in binding upon mTOR inhibition specifically at mRNAs containing a TOP-motif, suggesting a new model for how translational repression is selectively achieved upon mTOR inhibition.

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Mitch Guttman @mitchguttman.bsky.social · 26/07/2025

We identified an interaction between LARP1 and 18S rRNA located within the mRNA channel entry site on the 40S small ribosomal subunit and @jbquerido.bsky.social resolved this structure at 2.8 Å using single-particle cryo-EM.

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Mitch Guttman @mitchguttman.bsky.social · 26/07/2025

Single nucleotide binding maps generated by SPIDR can map known RNP structures at atomic resolution and identify novel components within RNP structures.

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Mitch Guttman @mitchguttman.bsky.social · 26/07/2025

We show that SPIDR generates high quality data across a diverse range of RBPs, including transcription, splicing, translation, and miRNA biogenesis, all within a single experiment.

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Mitch Guttman @mitchguttman.bsky.social · 26/07/2025

SPIDR uses a dramatically simplified split-and-pool based strategy to increase the throughput of CLIP by two orders of magnitude. SPIDR enables the rapid generation of consortium-level datasets within any molecular biology lab without the need for specialized training or equipment.

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Mitch Guttman @mitchguttman.bsky.social · 26/07/2025

Many proteins bind RNA, yet we still don’t know what RNAs most bind because methods map one RBP at a time. In @cp-cell.bsky.social, with the Jovanovic lab, we describe SPIDR – a method for mapping the RNA binding sites of dozens of RBPs in a single experiment. www.sciencedirect.com/science/arti...

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Mitch Guttman @mitchguttman.bsky.social · 27/11/2024

This work was led by co-first authors Drew Perez and Isabel Goronzy and our amazing team @caltech.edu, and funding from NHGRI.

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Mitch Guttman @mitchguttman.bsky.social · 27/11/2024

By enabling the generation of consortium-level datasets within any molecular biology lab, ChIP-DIP facilitates a fundamental transition from ‘reference-maps’ to context-specific maps and represents a transformative new tool for dissecting cell-type specific gene regulation.

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Mitch Guttman @mitchguttman.bsky.social · 27/11/2024

We used ChIP-DIP to explore quantitative combinations of histone modifications that define distinct classes of regulatory elements and integrated these signatures with regulatory factor binding to identify their functional activity.

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Mitch Guttman @mitchguttman.bsky.social · 27/11/2024

We used ChIP-DIP to measure temporal chromatin dynamics in primary mouse dendritic cells following stimulation and correlate these with transcriptional changes. For this, we mapped multiple time points within a single experiment, multiplexing across both proteins and samples.

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Mitch Guttman @mitchguttman.bsky.social · 27/11/2024

ChIP DIP generates highly accurate maps for ALL classes of DNA-associated proteins, including histone modifications, chromatin regulators, transcription factors, and RNA polymerases.

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Mitch Guttman @mitchguttman.bsky.social · 27/11/2024

ChIP-DIP uses a simple antibody-labeling strategy followed by split-and-pool barcoding to multiplex DNA-protein mapping. This enables the rapid generation of consortium-level datasets within any molecular biology lab without the need for specialized training or equipment.

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Mitch Guttman @mitchguttman.bsky.social · 27/11/2024

Gene regulation involves thousands of proteins that bind DNA, yet comprehensively mapping these is challenging. Our paper in Nature Genetics describes ChIP-DIP, a method for genome-wide mapping of hundreds of DNA-protein interactions in a single experiment. www.nature.com/articles/s41...

nature.com

ChIP-DIP maps binding of hundreds of proteins to DNA simultaneously and identifies diverse gene regulatory elements - Nature Genetics

ChIP-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...

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Reposted by Mitch Guttman

Josh Mendell @mendell-lab.bsky.social · 22/11/2024

Great thread on our paper from Jan👇

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Mitch Guttman @mitchguttman.bsky.social · 18/11/2024

A report made counterintuitive claims that PRC2 binds → more RNA than PTBP1 & hnRNPU → RNAs that do not exist in the cell We found a simple explanation: the authors ignore most RNA in the sample, leading to inflated background & misleading conclusions. www.biorxiv.org/content/10.1...

biorxiv.org

Failing to account for RNA quantity inflates background and leads to the misleading appearance that PRC2 and GFP bind to RNA in vivo

We recently published biochemical and quantitative evidence that challenges the widespread claims that PRC2 binds directly to many RNAs in vivo . A recent preprint performs a re-analysis of some of ou...

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Reposted by Mitch Guttman

Job Dekker @jobdekker.bsky.social · 14/11/2024

Leonid Mirny and I wrote this for all interested in chromosomes: "The chromosome folding problem and how cells solve it" www.cell.com/action/showP...

cell.com

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