Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
18 authors.
Eden EngalThe Lautenberg Center for Immunology and Cancer Research, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.ORCID 0000-0002-4353-6521
Aveksha SharmaDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.ORCID 0000-0002-2622-9386
Uria AvielThe Lautenberg Center for Immunology and Cancer Research, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.ORCID 0009-0008-0344-3540
Nadeen TaqatqaDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
Sarah JusterStem Cell Research Laboratory, Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.ORCID 0009-0007-4451-8417
Shiri Jaffe-HermanDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.ORCID 0009-0009-2297-1055
Mercedes BentataThe Lautenberg Center for Immunology and Cancer Research, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
Ophir GeminderDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.ORCID 0009-0004-1350-9487
Adi GershonDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
Reyut LewisThe Lautenberg Center for Immunology and Cancer Research, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
Gillian KayDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.ORCID 0000-0003-0966-2388
Merav HechtThe Lautenberg Center for Immunology and Cancer Research, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
Silvina Epsztejn-LitmanStem Cell Research Laboratory, Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.ORCID 0009-0002-7502-8609
Marc GotkineDepartment of Neurology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel.ORCID 0000-0003-2541-6232
Vincent MoulyUPMC University Paris 06, Inserm UMRS974, CNRS FRE3617, Center for Research in Myology, Sorbonne University,75252 Paris, France.ORCID 0000-0003-3809-4033
Rachel EigesStem Cell Research Laboratory, Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.ORCID 0000-0001-8139-0933
Maayan SaltonDepartment of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.ORCID 0000-0001-8812-5577
Yotam DrierThe Lautenberg Center for Immunology and Cancer Research, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.ORCID 0000-0003-1725-2995
Funding
No grant is acknowledged in the PubMed record.
6 · The paper itself
Abstract
Structural maintenance of chromosomes flexible hinge domain-containing 1 (SMCHD1) is a noncanonical SMC protein and an epigenetic regulator. Mutations in SMCHD1 cause facioscapulohumeral muscular dystrophy (FSHD), by overexpressing DUX4 in muscle cells. Here, we demonstrate that SMCHD1 is a key regulator of alternative splicing in various cell types. We show how SMCHD1 loss causes splicing alterations of DNMT3B, which can lead to hypomethylation and DUX4 overexpression. Analyzing RNA sequencing data from muscle biopsies of patients with FSHD and Smchd1 knocked out cells, we found mis-splicing of hundreds of genes upon SMCHD1 loss. We conducted a high-throughput screen of splicing factors, revealing the involvement of the splicing factor RBM5 in the mis-splicing of DNMT3B. Subsequent RNA immunoprecipitation experiments confirmed that SMCHD1 is required for RBM5 recruitment. Last, we show that mis-splicing of DNMT3B leads to hypomethylation of the D4Z4 region and to DUX4 overexpression. These results suggest that DNMT3B mis-splicing due to SMCHD1 loss plays a major role in FSHD pathogenesis.
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.
DNMT3B splicing dysregulation mediated by SMCHD1 loss contributes to DUX4 overexpression and FSHD pathogenesis. · full record | OpenQuestion