ArticleThe Journal of biological chemistry2014
Genomic determinants of gene regulation by 1,25-dihydroxyvitamin D3 during osteoblast-lineage cell differentiation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 103 citations in OpenAlex.
- The vitamin D receptor story: discovery, control, and genomic reach.The Journal of endocrinology · 2026Review
- Genome-wide chromatin profiling reveals a nonlimiting role for RXR in macrophage-like cells stimulated with multiple nuclear receptor agonists.The Journal of biological chemistry · 2026Article
- The neutrophil-osteogenic cell axis promotes bone destruction in periodontitis.International journal of oral science · 2024Article
- Genomic mechanisms controlling renal vitamin D metabolism.The Journal of steroid biochemistry and molecular biology · 2023Article
- Neuropilin 2 in osteoblasts regulates trabecular bone mass in male mice.Frontiers in endocrinology · 2023Article
- Molecular insights into mineralotropic hormone inter-regulation.Frontiers in endocrinology · 2023Review
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- Vitamin D and Its Target Genes.Nutrients · 2022Review
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- PTH, FGF-23, Klotho and Vitamin D as regulators of calcium and phosphorus: Genetics, epigenetics and beyond.Frontiers in endocrinology · 2022Review
- New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues.International journal of molecular sciences · 2021Review
- Vitamin K and D Supplementation and Bone Health in Chronic Kidney Disease-Apart or Together?Nutrients · 2021Review
- RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk.Cell death and differentiation · 2021Article
- Genomic Mechanisms Governing Mineral Homeostasis and the Regulation and Maintenance of Vitamin D Metabolism.JBMR plus · 2021Article
- Switches in histone modifications epigenetically control vitamin D3-dependent transcriptional upregulation of the CYP24A1 gene in osteoblastic cells.Journal of cellular physiology · 2020Article
- Ezh2-dependent H3K27me3 modification dynamically regulates vitamin D3-dependent epigenetic control of CYP24A1 gene expression in osteoblastic cells.Journal of cellular physiology · 2020Article
- VDR in salivary gland homeostasis and cancer.The Journal of steroid biochemistry and molecular biology · 2020Article
- New aspects of vitamin D metabolism and action - addressing the skin as source and target.Nature reviews. Endocrinology · 2020Review
- Vitamin D: Newer Concepts of Its Metabolism and Function at the Basic and Clinical Level.Journal of the Endocrine Society · 2020Article
- Article
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4 authors at 1 institution in 1 country.
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Abstract
The biological effects of 1α,25-dihydroxyvitamin D3 (1,25 (OH)2D3) on osteoblast differentiation and function differ significantly depending upon the cellular state of maturation. To explore this phenomenon mechanistically, we examined the impact of 1,25(OH)2D3 on the transcriptomes of both pre-osteoblastic (POBs) and differentiated osteoblastic (OBs) MC3T3-E1 cells, and assessed localization of the vitamin D receptor (VDR) at sites of action on a genome-scale using ChIP sequence analysis. We observed that the 1,25(OH)2D3-induced transcriptomes of POBs and OBs were quantitatively and qualitatively different, supporting not only the altered biology observed but the potential for a change in VDR interaction at the genome as well. This idea was confirmed through discovery that VDR cistromes in POBs and OBs were also strikingly different. Depletion of VDR-binding sites in OBs, due in part to reduced VDR expression, was the likely cause of the loss of VDR-target gene interaction. Continued novel regulation by 1,25(OH)2D3, however, suggested that factors in addition to the VDR might also be involved. Accordingly, we show that transcriptomic modifications are also accompanied by changes in genome binding of the master osteoblast regulator RUNX2 and the chromatin remodeler CCAAT/enhancer-binding protein β. Importantly, genome occupancy was also highlighted by the presence of epigenetic enhancer signatures that were selectively changed in response to both differentiation and 1,25(OH)2D3. The impact of VDR, RUNX2, and C/EBPβ on osteoblast differentiation is exemplified by their actions at the Runx2 and Sp7 gene loci. We conclude that each of these mechanisms may contribute to the diverse actions of 1,25(OH)2D3 on differentiating osteoblasts.
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Registered trials
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