1. Functional characterization of the SDR42E1 reveals its role in vitamin D biosynthesis
- Author
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Nagham Nafiz Hendi, Maria Teresa Bengoechea-Alonso, Johan Ericsson, and Georges Nemer
- Subjects
SDR42E1 ,Vitamin D biosynthesis ,Steroidogenesis ,CRISPR/Cas9 ,Multi-omics ,HaCaT ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Vitamin D deficiency poses a widespread health challenge, shaped by environmental and genetic determinants. A recent discovery identified a genetic regulator, rs11542462, in the SDR42E1 gene, though its biological implications remain largely unexplored. Our bioinformatic assessments revealed pronounced SDR42E1 expression in skin keratinocytes and the analogous HaCaT human keratinocyte cell lines, prompting us to select the latter as an experimental model. Employing CRISPR/Cas9 gene-editing technology and multi-omics approach, we discovered that depleting SDR42E1 showed a 1.6-fold disruption in steroid biosynthesis pathway (P-value = 0.03), considerably affecting crucial vitamin D biosynthesis regulators. Notably, SERPINB2 (P-value = 2.17 × 10−103), EBP (P-value = 2.46 × 10−13), and DHCR7 (P-value = 8.03 × 10−09) elevated by ∼2–3 fold, while ALPP (P-value
- Published
- 2024
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