Enrichment of Cis -Acting Regulatory Elements in Differentially Methylated Regions Following Lipopolysaccharide Treatment of Bovine Endometrial Epithelial Cells

• Published in: International journal of molecular sciences Vol. 25; no. 18; p. 9832
• Main Authors: Jhamat, Naveed, Guo, Yongzhi, Han, Jilong, Humblot, Patrice, Bongcam-Rudloff, Erik, Andersson, Göran, Niazi, Adnan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.09.2024; MDPI
• Subjects: Animal reproduction; Animals; Bacterial infections; Binding Sites; Bioinformatics; Cattle; Cells, Cultured; cis-acting regulatory element; Dairy cattle; Development and progression; Developmental Biology; differential DNA methylation; DNA Methylation; E coli; Endometritis; Endometritis - genetics; Endometritis - metabolism; Endometrium; Endometrium - metabolism; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Female; Gene expression; gene regulation; Genetic aspects; Genomes; Genomics; Health aspects; Inflammation; Lipopolysaccharides; LPS; Organisms; Physiological aspects; Promoters (Genetics); Proteins; Regulatory Sequences, Nucleic Acid; RNA polymerase; transcription factor binding sites; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; transcriptional networks; Utvecklingsbiologi; Sweden; cis-acting regulatory element; transcription factor binding sites; gene regulation; differential DNA methylation; LPS; transcriptional networks
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25189832

Endometritis is an inflammatory disease that negatively influences fertility and is common in milk-producing cows. An in vitro model for bovine endometrial inflammation was used to identify enrichment of -acting regulatory elements in differentially methylated regions (DMRs) in the genome of in vitro-cultured primary bovine endometrial epithelial cells (bEECs) before and after treatment with lipopolysaccharide (LPS) from , a key player in the development of endometritis. The enriched regulatory elements contain binding sites for transcription factors with established roles in inflammation and hypoxia including NFKB and Hif-1α. We further showed co-localization of certain enriched -acting regulatory motifs including ARNT, Hif-1α, and NRF1. Our results show an intriguing interplay between increased mRNA levels in LPS-treated bEECs of the mRNAs encoding the key transcription factors such as AHR, EGR2, and STAT1, whose binding sites were enriched in the DMRs. Our results demonstrate an extraordinary -regulatory complexity in these DMRs having binding sites for both inflammatory and hypoxia-dependent transcription factors. Obtained data using this in vitro model for bacterial-induced endometrial inflammation have provided valuable information regarding key transcription factors relevant for clinical endometritis in both cattle and humans.