{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:26:48Z","timestamp":1760146008376,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU projects \u201cPROLIFIC\u201d","award":["311776-PR","2015-888"],"award-info":[{"award-number":["311776-PR","2015-888"]}]},{"name":"FORMAS","award":["311776-PR","2015-888"],"award-info":[{"award-number":["311776-PR","2015-888"]}]},{"name":"Swedish University of Agricultural Sciences","award":["311776-PR","2015-888"],"award-info":[{"award-number":["311776-PR","2015-888"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 cis-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 E. coli, 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-1\u03b1. We further showed co-localization of certain enriched cis-acting regulatory motifs including ARNT, Hif-1\u03b1, 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 cis-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.<\/jats:p>","DOI":"10.3390\/ijms25189832","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T10:33:01Z","timestamp":1726050781000},"page":"9832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enrichment of Cis-Acting Regulatory Elements in Differentially Methylated Regions Following Lipopolysaccharide Treatment of Bovine Endometrial Epithelial Cells"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9876-4262","authenticated-orcid":false,"given":"Naveed","family":"Jhamat","sequence":"first","affiliation":[{"name":"Department of Animal Biosciences, Swedish University of Agricultural Sciences, P.O. Box 7023, SE-75007 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5057-9095","authenticated-orcid":false,"given":"Yongzhi","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Swedish University of Agricultural Sciences, P.O. Box 7023, SE-75007 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9747-8163","authenticated-orcid":false,"given":"Jilong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Animal Biosciences, Swedish University of Agricultural Sciences, P.O. Box 7023, SE-75007 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5292-1798","authenticated-orcid":false,"given":"Patrice","family":"Humblot","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Swedish University of Agricultural Sciences, P.O. Box 7023, SE-75007 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1947-8288","authenticated-orcid":false,"given":"Erik","family":"Bongcam-Rudloff","sequence":"additional","affiliation":[{"name":"Department of Animal Biosciences, Swedish University of Agricultural Sciences, P.O. Box 7023, SE-75007 Uppsala, Sweden"},{"name":"SLU-Global Bioinformatics Centre, Swedish University of Agricultural Sciences, P.O. 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