ArticleMolecular and cellular biology1999
Multiple Cbfa/AML sites in the rat osteocalcin promoter are required for basal and vitamin D-responsive transcription and contribute to chromatin organization.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 139 citations in OpenAlex.
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- Epigenetic-Mediated Regulation of Gene Expression for Biological Control and Cancer: Cell and Tissue Structure, Function, and Phenotype.Results and problems in cell differentiation · 2022Review
- Inhibition of the epigenetic suppressor EZH2 primes osteogenic differentiation mediated by BMP2.The Journal of biological chemistry · 2020Article
- miR‑483‑3p regulates osteogenic differentiation of bone marrow mesenchymal stem cells by targeting STAT1.Molecular medicine reports · 2019Article
- Induction of ALP and MMP9 activity facilitates invasive behavior in heterogeneous human BMSC and HNSCC 3D spheroids.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
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- Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology.Disease models & mechanisms · 2016Article
- Transcriptional Auto-Regulation of RUNX1 P1 Promoter.PloS one · 2016Article
- Epigenetic Mechanisms Regulating Mesenchymal Stem Cell Differentiation.Current genomics · 2015Article
- Histone H3 lysine 36 methyltransferase Whsc1 promotes the association of Runx2 and p300 in the activation of bone-related genes.PloS one · 2014Article
- Genomic occupancy of HLH, AP1 and Runx2 motifs within a nuclease sensitive site of the Runx2 gene.Journal of cellular physiology · 2013Article
- Reduced osteoblast activity in the mice lacking TR4 nuclear receptor leads to osteoporosis.Reproductive biology and endocrinology : RB&E · 2012Article
- Genome-wide Runx2 occupancy in prostate cancer cells suggests a role in regulating secretion.Nucleic acids research · 2012Article
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- Genetic and transcriptional control of bone formation.Oral and maxillofacial surgery clinics of North America · 2010Review
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- Prolactin blocks nuclear translocation of VDR by regulating its interaction with BRCA1 in osteosarcoma cells.Molecular endocrinology (Baltimore, Md.) · 2009Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Three Cbfa motifs are strategically positioned in the bone-specific rat osteocalcin (rOC) promoter. Sites A and B flank the vitamin D response element in the distal promoter and sites B and C flank a positioned nucleosome in the proximal promoter. The functional significance of each Cbfa element was addressed by mutating individual or multiple Cbfa sites within the context of the -1.1-kb rOC promoter fused to a chloramphenicol acetyltransferase reporter gene. Promoter activity was assayed following transient transfection and after stable genomic integration in ROS 17/2.8 osteoblastic cell lines. We show that all three Cbfa sites are required for maximal basal expression of the rOC promoter. However, the distal sites A and B each contribute significantly more (P < 0.001) to promoter activity than site C. In a genomic context, sites A and B can largely compensate for a mutation at the proximal site C, and paired mutations involving site A (mAB or mAC) result in a far greater loss of activity than the mBC mutation. Strikingly, mutation of the three Cbfa sites leads to abrogation of responsiveness to vitamin D. Vitamin D-enhanced activity is also not observed when sites A and B are mutated. Significantly, related to these losses in transcriptional activity, mutation of the three Cbfa sites results in altered chromatin structure as reflected by loss of DNase I-hypersensitive sites at the vitamin D response element and over the proximal tissue-specific basal promoter. These findings strongly support a multifunctional role for Cbfa factors in regulating gene expression, not only as simple transcriptional transactivators but also by facilitating modifications in promoter architecture and chromatin organization.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.