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Blimp1/Prdm1 Functions in Opposition to Irf1 to Maintain Neonatal Tolerance during Postnatal Intestinal Maturation


The transcriptional repressor Blimp1/Prdm1 plays a pivotal role in the metabolic switch that occurs in the small intestine during the suckling to weaning transition. Notably, expression profiling of perinatal Blimp1-deficient small intestine revealed premature activation of metabolic genes normally restricted to post-weaning enterocytes. To further elucidate the function of Blimp1 in intestinal development, we engineered a novel Blimp1-eGFP-fusion knock-in mouse strain to perform ChIP-seq analysis. In addition to identifying which metabolic genes are direct Blimp1 targets, ChIP-seq analysis revealed a highly conserved Blimp1/Irf-1 overlapping sites that function to control MHC class I antigen processing during acquisition of neonatal tolerance in the first weeks after birth during early colonization of the intestinal tract by commensal microorganisms. Moreover, immunohistochemical analysis of human fetal intestine suggests that a BLIMP1/IRF-1 axis may also function in human intestinal epithelium development.


Vyšlo v časopise: Blimp1/Prdm1 Functions in Opposition to Irf1 to Maintain Neonatal Tolerance during Postnatal Intestinal Maturation. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005375
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005375

Souhrn

The transcriptional repressor Blimp1/Prdm1 plays a pivotal role in the metabolic switch that occurs in the small intestine during the suckling to weaning transition. Notably, expression profiling of perinatal Blimp1-deficient small intestine revealed premature activation of metabolic genes normally restricted to post-weaning enterocytes. To further elucidate the function of Blimp1 in intestinal development, we engineered a novel Blimp1-eGFP-fusion knock-in mouse strain to perform ChIP-seq analysis. In addition to identifying which metabolic genes are direct Blimp1 targets, ChIP-seq analysis revealed a highly conserved Blimp1/Irf-1 overlapping sites that function to control MHC class I antigen processing during acquisition of neonatal tolerance in the first weeks after birth during early colonization of the intestinal tract by commensal microorganisms. Moreover, immunohistochemical analysis of human fetal intestine suggests that a BLIMP1/IRF-1 axis may also function in human intestinal epithelium development.


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