The HP1γ epigenetic silencer dampens IFN-γ response at the gut epithelial barrier
Chang, Y.; Mata-Garrido, J.; desterke, C.; Batsche, E.; Hamai, A.; Youssouf, S.; Skurnik, D.; Jalil, A.; Beche, J.-C.; Piaggio, E.; Arbibe, L.; Marchand, Y. C.
Show abstract
Interferon gamma (IFN-{gamma}) plays central roles in the pathophysiology of inflammatory bowel disease (IBD), both activating inflammatory responses and immunosuppressive functions. However, the epigenetic mechanisms controlling the expression of IFN-{gamma} responsive genes at the gut epithelial barrier are not well understood. In this study, we identified the epigenetic regulator HP1{gamma} as a transcriptional repressor of the IFN-{gamma}-responsive genes STAT1 (signal transducer and activator of transcription 1) and PD-L1 (Programmed Cell Death Ligand 1). Accordingly, HP1{gamma} gene inactivation in the mouse gut epithelium resulted in an immunopathology with a long-lasting up-regulation of STAT1 and PD-L1. Colon organoids models and in vitro cell lines showed that HP1{gamma} deficiency primed STAT1 and PD-L1 expressions, ultimately sensitizing epithelial cells to IFN-{gamma} stimulation. Chromatin immunoprecipitation experiments suggest that HP1 promoter tethering is involved in the silencing of gene expression. Overall, these results identify HP1{gamma} as an epigenetic silencing pathway controlling the IFN-{gamma} response at the epithelial barrier.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A Ctnnb1 enhancer transcriptionally regulates Wnt signaling dosage to balance homeostasis and tumorigenesis of intestinal epithelia 96%
- TBX3 acts as tissue-specific component of the Wnt/β-catenin enhanceosome 94%
- A hepatocyte-specific transcriptional program driven by Rela and Stat3 exacerbates experimental colitis in mice by modulating bile synthesis 94%
Similar papers in this journal
- Lysophosphatidic acid-mediated GPR35 signaling in CX3CR1+ macrophages regulates the intestinal cytokine milieu 95%
- Yap1-driven intestinal repair is controlled by group 3 innate lymphoid cells 94%
- p57Kip2 acts as a transcriptional corepressor to regulate intestinal stem cell fate and proliferation 94%
Similar papers in this journal
Similar papers in this journal
- Creb Regulates Foxp3+St-2+ Tregs With Enhanced Il-10 Production 95%
- Sustained post-developmental T-bet expression is critical for the maintenance of type 1 innate lymphoid cells in vivo 94%
- Multiple environmental signaling pathways control the differentiation of RORγt-expressing regulatory T cells 94%
Similar papers in this journal
- E prostanoid receptor 4 expressing macrophages promote the regeneration of the intestinal epithelial barrier upon inflammation 95%
- CARD9 in Neutrophils Protects from Colitis and Controls Mitochondrial Metabolism and Cell Survival 94%
- Genetic variation at 11q23.1 confers colorectal cancer risk by dysregulation of colonic tuft cell transcriptional activator POU2AF2 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.