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| Status |
Public on Jun 02, 2014 |
| Title |
Genomic Determinants of Gene Regulation by 1,25-Dihydroxyvitamin D3 During Osteoblast-Lineage Cell Differentiation [gene expression] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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-seq 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 C/EBPβ. Importantly, genome occupancy was also highlighted by the presence of epigenetic enhancer signatures which 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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| Overall design |
RNA was isolated and applied to gene expression microarrays in undifferentiated MC3T3-E1 cells as well as post 15 day osteogenic differentiation MC3T3-E1 cells, which were treated for 24 hours with 10-7M 1,25(OH)2D3. For the vehicle matched samples, please refer to study GSE41955. The samples were completed in biological triplicate.
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| Contributor(s) |
Meyer MB, Benkusky NA, Pike JW |
| Citation(s) |
24891508 |
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| Submission date |
Oct 21, 2013 |
| Last update date |
Jun 05, 2014 |
| Contact name |
Mark B Meyer |
| E-mail(s) |
markmeyer@wisc.edu
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| Phone |
608-890-0857
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| Organization name |
University of Wisconsin-Madison
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| Department |
Nutritional Sciences
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| Lab |
Meyer Lab
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| Street address |
1415 Linden Dr.
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| City |
Madison |
| State/province |
WI |
| ZIP/Postal code |
53706 |
| Country |
USA |
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| Platforms (1) |
| GPL13179 |
NimbleGen mouse expression array (2006-08-03_MM8_60mer_expr) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE51515 |
Genomic Determinants of Gene Regulation by 1,25-Dihydroxyvitamin D3 During Osteoblast-Lineage Cell Differentiation |
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| Relations |
| BioProject |
PRJNA224719 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE51514_RAW.tar |
76.8 Mb |
(http)(custom) |
TAR (of CALLS, PAIR) |
| Processed data included within Sample table |
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