The Journal of Clinical Investigation’s Post

#MultiomicsPapers Challenge!🔥🔥👏👏 A great recent study on Chronic Kidney Disease (CKD) and Metabolic dysfunction-associated steatohepatitis (MASH) highlights the importance of integrating different modalities of transcriptomic data for a better understanding of molecular mechanisms. By combining single-cell (scRNAseq) and spatial transcriptomics (ST), they identified pivotal information about signaling pathways in #CKD and #MASH. These novel findings could pave the way for the identification of future potential therapeutic targets and developing effective therapies. #multiomics #scRNA #transcriptomics Join us in the #multiomicspapers challenge and stay tuned for more updates! Kudos to Vivek Das, PhD, M.Sc. and all the authors!

Our latest paper with proteomic profiling in mice with persistent #AFib revealed that fibrotic remodeling begins at molecular levels much earlier than its clinical manifestation. Targeting these proteins preemptively may result in better prognosis for these patients! https://lnkd.in/gDbr5GB2

Did everyone see this article where the authors develop Chrom-seq, a method free of both crosslinking and antibody, to identify RNAs associated with epigenetically modified chromatin? Nice work to you and your team Professor Yan. https://lnkd.in/eqPj9wN5 Chad Pecot, UNC RNA Discovery Center, Science, Jian Yan

I am happy to share our new publication in Nature: Promotion of DNA end resection by BRCA1–BARD1 in homologous recombination. In simple words- Using a combination of biochemical, single-molecule, and cellular methods, we discovered new roles of the BRCA1-BARD1 tumor suppressor in promoting DNA end processing/ trimming (by the enzymes BLM/WRN-DNA2 and EXO1) in species-specific manner. This is an important step in the early repair of double-strand DNA breaks through the homologous recombination pathway. BRCA1-BARD1 interacts directly with both DNA and the enzymes involved in this process, likely acting as a scaffold. Mutations that affect its ability to bind DNA restrict this function. Happy reading!!

Understanding how the genome's arrangement and structure regulate gene expression could unlock new insights into human biology and disease. Kyung Lock Kim, Anders Sejr Hansen, Bradley Bernstein, and others deeply characterized a topological boundary, disrupted in gastrointestinal stromal tumors (GIST), that insulates potent FGF ligand oncogenes from a nearby enhancer. The researchers found that redundant CCCTC-binding factor (CTCF) binding sites in the boundary help robustly insulate the FGF oncogenes from the surrounding genome. Their findings support a model in which long-range transcriptional activation in GIST is driven by stable physical interaction between enhancer and promoter initiation sites. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

In continuation of our exploration into the dynamic world of #ATP-#dependent #chromatin remodeling with the #SWI/SNF complex, #enhancers, and #gene #transcription, I am thrilled to present our findings, recently published in #Molecular #Cell. Our study unveils, for the first time, the remarkable role of #enhancer #RNAs (#eRNAs) in orchestrating the #recruitment of the #SWI/SNF complex to stage-specific #enhancers, including #typical #enhancers and #super-#enhancers. In a revelatory discovery, we demonstrate that #eRNAs serve as pivotal facilitators in guiding the #SWI/SNF complex to its target sites. Moreover, our investigation reveals that the #AT-hook motif of #BRG1 (the ATPase subunit of the SWI/SNF complex), exhibits a distinct preference for binding to #enhancer #RNA over #DNA. This novel finding underscores the intricate molecular interplay driving chromatin dynamics. Furthermore, our study elucidates that the #AT-hook motif of #BRG1 is not only crucial for its interaction with #enhancer #RNA but also essential for the #recruitment of key #transcriptional #co-activators, including #MLL3/4, #Med1, and #p300/CBP. This intricate network of molecular interactions highlights the multifaceted nature of chromatin regulation and #gene #expression. The implications of our findings are profound, offering a new perspective on the mechanisms underlying #SWI/SNF recruitment to enhancer regions. By identifying #enhancer #RNAs as precursors in this recruitment process, our work opens avenues for targeted interventions aimed at modulating aberrant SWI/SNF function in various diseases. Here is the link - https://lnkd.in/gCh6iTXT

Neumann et al. developed a compact epigenetic silencer called CHARM, that, when delivered systemically via a viral vector, effectively shut down prion genes throughout the mouse brain without altering the underlying DNA sequence. The epigenetic editor can also be programmed to turn themselves off after silencing its target, limiting the potential adverse effects of long-term expression. Read the article on Science to learn more about this research: https://lnkd.in/eZ9xJwvv Edwin Neumann Tessa Bertozzi #AAVmediated #epigeneticeditor #genesilencing #Priondisease

It would be great to see this application of Prime Editing moving onto a clinical trial! #crispr #crisprcas9 #primeediting #genetherapy #geneediting #genomeediting #crisprmedicine #crisprtherapeutics

🩸 🩸 🩸 𝐁𝐚𝐬𝐞 𝐄𝐝𝐢𝐭𝐢𝐧𝐠 𝐂𝐨𝐫𝐫𝐞𝐜𝐭𝐬 𝐂𝐨𝐦𝐦𝐨𝐧 𝐇𝐚𝐞𝐦𝐨𝐩𝐡𝐢𝐥𝐢𝐚 𝐀 𝐌𝐮𝐭𝐚𝐭𝐢𝐨𝐧𝐬 𝐚𝐧𝐝 𝐑𝐞𝐬𝐭𝐨𝐫𝐞𝐬 𝐅𝐚𝐜𝐭𝐨𝐫 𝐕𝐈𝐈𝐈 𝐄𝐱𝐩𝐫𝐞𝐬𝐬𝐢𝐨𝐧 𝐢𝐧 𝐃𝐢𝐬𝐞𝐚𝐬𝐞 𝐌𝐨𝐝𝐞𝐥𝐬 🩸 🩸 🩸  Scientists at University of Ferrara and Università degli Studi del Piemonte Orientale in Italy have demonstrated that DNA base editing corrects common haemophilia A mutations and restores factor VIII expression in in vitro and ex vivo models of disease. https://lnkd.in/eVkvfFW5 #crisprmedicinenews #crisprmedicine #crispr #baseediting #primeediting #geneediting #haemophilia #raredisease #blooddisease