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| Item Type: | Preprint |
|---|---|
| Title: | Genetic analysis of cis-enhancers associated with bone mineral density and periodontitis in the gene SOST |
| Creators Name: | Chopra, A., Song, J., Weiner 3rd, J., Beule, D. and Schaefer, A.S. |
| Abstract: | A haplotype block at the sclerostin (SOST) 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 quanti ed disease-related enhancer activities regulating SOST expression. Additionally, in SaOS-2 cells, we investigated the in uence 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 signi cant cis-activating effect (25-fold change in SOST expression), with the C-allele containing a CEBPB binding motif (position weight matrix (PWM) = 0.98, P(corrected) = 7.7 x 10(−7)). CEBPB knockdown induced genome-wide upregulation but decreased epithelialmesenchymal transition genes (P = 0.71, AUC = 2.2 x 10(−11)). This study identi es a robust SOST cisactivating element linked to BMD and periodontitis, carrying CEBPB binding sites, and highlights CEBPB's impact on epithelial-mesenchymal transition. |
| Keywords: | Periodontitis, Bone Mineral Density, SOST, Causal Variant, Rs9783823, CEBPB, Animals, Mice |
| Source: | Research Square |
| Publisher: | Research Square |
| Article Number: | rs.3.rs-4409923 |
| Date: | 20 June 2024 |
| Official Publication: | https://doi.org/10.21203/rs.3.rs-4409923/v1 |
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