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Series GSE62978 Query DataSets for GSE62978
Status Public on Nov 14, 2014
Title The Parathyroid Hormone-Regulated Transcriptome in Osteocytes: Parallel Actions with 1,25-Dihydroxyvitamin D3 to Oppose Gene Expression Changes During Differentiation and to Promote Mature Cell Function [ChIP-Seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Although localized to the mineralized matrix of bone, osteocytes are able to respond to systemic factors such as the calciotropic hormones 1,25(OH)2D3 and PTH. In the present studies, we examine the transcriptomic response to PTH in an osteocyte cell model and found that this hormone regulated an extensive panel of genes. Surprisingly, PTH uniquely modulated two cohorts of genes, one that was expressed and associated with the osteoblast to osteocyte transition and the other a cohort that was expressed only in the mature osteocyte. Interestingly, PTH’s effects were largely to oppose the expression of differentiation-related genes in the former cohort, while potentiating the expression of osteocyte-specific genes in the latter cohort. A comparison of the transcriptional effects of PTH with those obtained previously with 1,25(OH)2D3 revealed a subset of genes that was strongly overlapping. While 1,25(OH)2D3 potentiated the expression of osteocyte-specific genes similar to that seen with PTH, the overlap between the two hormones was more limited. Additional experiments identified the PKA-activated phospho-CREB (pCREB) cistrome, revealing that while many of the differentiation-related PTH regulated genes were apparent targets of a PKA-mediated signaling pathway, a reduction in pCREB binding at sites associated with osteocyte-specific PTH targets appeared to involve alternative PTH activation pathways. That pCREB binding activities positioned near important hormone-regulated gene cohorts were localized to control regions of genes was reinforced by the presence of epigenetic enhancer signatures exemplified by unique modifications at histones H3 and H4. These studies suggest that both PTH and 1,25(OH)2D3 may play important and perhaps cooperative roles in limiting osteocyte differentiation from its precursors while simultaneously exerting distinct roles in regulating mature osteocyte function. Our results provide new insight into transcription factor-associated mechanisms through which PTH and 1,25(OH)2D3 regulate a plethora of genes important to the osteoblast/osteocyte lineage.
 
Overall design ChIP-seq was performed on MC3T3-E1 cells for Phospho-Creb following 1 hour vehicle or forskolin treatment in biological replicate. Input sample was previously published in GSE41920 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM1027508).
 
Contributor(s) St. John HC, Meyer MB, Pike JW
Citation(s) 25460572
Submission date Nov 04, 2014
Last update date May 15, 2019
Contact name Mark B Meyer
E-mail(s) markmeyer@wisc.edu
Phone 608-890-0857
Organization name University of Wisconsin-Madison
Department Nutritional Sciences
Lab Meyer Lab
Street address 1415 Linden Dr.
City Madison
State/province WI
ZIP/Postal code 53706
Country USA
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (4)
GSM1537596 pCREB_Veh_rep1_MC3T3-E1
GSM1537597 pCREB_Veh_rep2_MC3T3-E1
GSM1537598 pCREB_Fsk_rep1_MC3T3-E1
This SubSeries is part of SuperSeries:
GSE62981 The Parathyroid Hormone-Regulated Transcriptome in Osteocytes: Parallel Actions with 1,25-Dihydroxyvitamin D3 to Oppose Gene Expression Changes During Differentiation and to Promote Mature Cell Function
Relations
BioProject PRJNA266330
SRA SRP049516

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Supplementary file Size Download File type/resource
GSE62978_RAW.tar 246.2 Mb (http)(custom) TAR (of BED, BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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