{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T05:10:29Z","timestamp":1742879429285,"version":"3.40.2"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>A haplotype block at the sclerostin (<jats:italic>SOST<\/jats:italic>) gene correlates with bone mineral density (BMD) and increased periodontitis risk in smokers. Investigating the putative causal variants within this block, our study aimed to elucidate the impact of linked enhancer elements on gene expression and to evaluate their role in transcription factor (TF) binding. Using CRISPR\/dCas9 activation (CRISPRa) screening in SaOS-2 cells, we quantified disease-related enhancer activities regulating <jats:italic>SOST<\/jats:italic> expression. Additionally, in SaOS-2 cells, we investigated the influence of the candidate TFs CCAAT\/enhancer-binding protein beta (CEBPB) on gene expression by antisense (GapmeR) knockdown, followed by RNA sequencing. The periodontitis-linked SNP rs9783823 displayed a significant cis-activating effect (25-fold change in <jats:italic>SOST<\/jats:italic> expression), with the C-allele containing a CEBPB binding motif (position weight matrix (PWM) =\u2009 0.98, P<jats:sub>corrected<\/jats:sub> =\u2009 7.7 x 10<jats:sup>-7<\/jats:sup>). <jats:italic>CEBPB<\/jats:italic> knockdown induced genome-wide upregulation but decreased epithelial-mesenchymal transition genes (P =\u2009 0.71, AUC =\u2009 2.2 x 10<jats:sup>-11<\/jats:sup>). This study identifies a robust <jats:italic>SOST<\/jats:italic> cis-activating element linked to BMD and periodontitis, carrying CEBPB binding sites, and highlights <jats:italic>CEBPB<\/jats:italic>\u2019s impact on epithelial-mesenchymal transition.<\/jats:p>","DOI":"10.1371\/journal.pone.0319259","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T04:37:18Z","timestamp":1742877438000},"page":"e0319259","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic analysis of cis-enhancers associated with bone mineral density and periodontitis in the gene 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