Mo1754 Early Life Environment Interacts With Genetic Risk in Inflammatory Bowel Diseases

Abstract

CEACAM6 gene promoter in an open chromatin state region characterized by increased H3S10 phosphorylation level. In contrast, Caco-2 cells expressed low levels of CEACAM6 due to a compact chromatin state in CEACAM6 promoter (low level of H3S10p). AIEC infection led to an increase in CEACAM6 expression related to enhanced HIF-1a binding to CEACAM6 promoter. Abnormal H3S10 phosphorylation in CEACAM6 promoter following AIEC infection enhanced HIF-1a binding and subsequent CEACAM6 expression. Moreover, in silico analysis predicted several miRNAs that are potentially able to regulate CEACAM6 expression. Luciferase reporter assays showed that among the predictive miRNAs, miR-765 and miR-29b-2-5p directly bound to the 3'-UTR of CEACAM6 mRNA. After AIEC infection, a down-regulation of miR-765 and an up-regulation of miR-29b-2-5p in T84 cells were observed. This is consistent with the observation that miR-765 decreased CEACAM6 protein expression compared to miR-29b-2-5p after transfection in T84 cells. Conclusion: This study suggests that AIEC bacteria have the ability to modulate gene expression in the host cell for their own benefit by altering different epigenetic marks as miRNA expression profile and histones post-translational modifications enhancing CEACAM6 abnormal expression. Thus, epigenetic pathways could be new targets to prevent AIEC colonization and AIECinduced inflammation in CD patients.