ArticleCell2022
Epigenetic reader SP140 loss of function drives Crohn's disease due to uncontrolled macrophage topoisomerases.
Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- CYTOKINE SIGNALING REGULATES MULTIPLE STAGES OF GAMMA-HERPESVIRUS INFECTION IN MYELOID CELLS.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic regulation of transgenes.Journal of biotechnology · 2026Review
- RNF2 mediates H2A ubiquitination to promote colitis via suppressing monocyte-macrophage transition in mice.Nature communications · 2026Article
- An SP110-SP100 axis is a critical regulator of promyelocytic leukaemia body dynamics and mitotic fidelity.Nature cell biology · 2026Article
- A convenient single-cell assay for the newly synthesized transcriptome reveals FLI1 regulon downregulation during T cell activation.Cell reports methods · 2026Article
- Macrophage dysregulation in inflammatory bowel disease: cellular heterogeneity, pathogenic mechanism, and treatment.Frontiers in immunology · 2026Review
- Host Genetic Architecture between Epstein-Barr Virus Activity and Multiple Sclerosis Reveals Shared Pathways.medRxiv : the preprint server for health sciences · 2025Article
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- Sp140L functions as a herpesvirus restriction factor suppressing viral transcription and activating interferon-stimulated genes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression.Nature communications · 2025Article
- The SP140-RESIST pathway regulates interferon mRNA stability and antiviral immunity.bioRxiv : the preprint server for biology · 2025Article
- Eleven Grand Challenges for Inflammatory Bowel Disease Genetics and Genomics.Inflammatory bowel diseases · 2025Review
- Topoisomerase-modulated genome-wide DNA supercoiling domains colocalize with nuclear compartments and regulate human gene expression.Nature structural & molecular biology · 2025Article
- Cellular senescence defining the disease characteristics of Crohn's disease.Frontiers in immunology · 2025Article
- An endogenous retrovirus regulates tumor-specific expression of the immune transcriptional regulator SP140.Human molecular genetics · 2024Article
- DNA topology: A central dynamic coordinator in chromatin regulation.Current opinion in structural biology · 2024Review
- Epigenetic regulation of innate immune dynamics during inflammation.Journal of leukocyte biology · 2024Review
- A CIC-related-epigenetic factors-based model associated with prediction, the tumor microenvironment and drug sensitivity in osteosarcoma.Scientific reports · 2024Article
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Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
How mis-regulated chromatin directly impacts human immune disorders is poorly understood. Speckled Protein 140 (SP140) is an immune-restricted PHD and bromodomain-containing epigenetic "reader," and SP140 loss-of-function mutations associate with Crohn's disease (CD), multiple sclerosis (MS), and chronic lymphocytic leukemia (CLL). However, the relevance of these mutations and mechanisms underlying SP140-driven pathogenicity remains unexplored. Using a global proteomic strategy, we identified SP140 as a repressor of topoisomerases (TOPs) that maintains heterochromatin and macrophage fate. In humans and mice, SP140 loss resulted in unleashed TOP activity, de-repression of developmentally silenced genes, and ultimately defective microbe-inducible macrophage transcriptional programs and bacterial killing that drive intestinal pathology. Pharmacological inhibition of TOP1/2 rescued these defects. Furthermore, exacerbated colitis was restored with TOP1/2 inhibitors in Sp140
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Registered trials
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.