ArticleThe Journal of biological chemistry2015
Selective Distal Enhancer Control of the Mmp13 Gene Identified through Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Genomic Deletions.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 59 citations in OpenAlex.
- The vitamin D receptor story: discovery, control, and genomic reach.The Journal of endocrinology · 2026Review
- METTL14 regulates chondrogenesis through the GDF5-RUNX-extracellular matrix gene axis during limb development.Nature communications · 2025Article
- "A Friend Among Strangers" or the Ambiguous Roles of Runx2.Biomolecules · 2024Review
- Runt-related Transcription Factors and Gene Regulatory Mechanisms in Skeletal Development and Diseases.Current osteoporosis reports · 2023Review
- Genomic mechanisms controlling renal vitamin D metabolism.The Journal of steroid biochemistry and molecular biology · 2023Article
- New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues.International journal of molecular sciences · 2021Review
- Discover novel disease-associated genes based on regulatory networks of long-range chromatin interactions.Methods (San Diego, Calif.) · 2021Article
- Article
- Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation.Epigenetics · 2021Article
- Runx2 plays a central role in Osteoarthritis development.Journal of orthopaedic translation · 2020Review
- Switches in histone modifications epigenetically control vitamin D3-dependent transcriptional upregulation of the CYP24A1 gene in osteoblastic cells.Journal of cellular physiology · 2020Article
- Vitamin D: Newer Concepts of Its Metabolism and Function at the Basic and Clinical Level.Journal of the Endocrine Society · 2020Article
- Mechanistic homeostasis of vitamin D metabolism in the kidney through reciprocal modulation of Cyp27b1 and Cyp24a1 expression.The Journal of steroid biochemistry and molecular biology · 2020Review
- A chromatin-based mechanism controls differential regulation of the cytochrome P450 geneThe Journal of biological chemistry · 2019Article
- Targeted genomic deletions identify diverse enhancer functions and generate a kidney-specific, endocrine-deficientThe Journal of biological chemistry · 2019Article
- Vitamin D in the Prevention and Treatment of Osteoarthritis: From Clinical Interventions to Cellular Evidence.Nutrients · 2019Review
- Recent advances in understanding the regulation of metalloproteinases.F1000Research · 2019Review
- New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration.Cells · 2018Article
- CRISPR-based strategies for studying regulatory elements and chromatin structure in mammalian gene control.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Review
- The potential of CRISPR/Cas9 genome editing for the study and treatment of intervertebral disc pathologies.JOR spine · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Matrix metalloproteinase 13 (Mmp13, collagenase-3) plays an essential role in bone metabolism and mineral homeostasis. It is regulated by numerous factors, including BMP-2, parathyroid hormone, and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), through transcription factors such as Runt-related transcription factor 2 (RUNX2), CCAAT/enhancer-binding protein β (C/EBPβ), OSX, and vitamin D receptor (VDR). During osteoblast maturation, the basal expression of Mmp13 and its sensitivity to 1,25(OH)2D3 are strikingly increased. In this report, ChIP-sequencing analysis in mouse preosteoblasts revealed that the Mmp13 gene was probably regulated by three major enhancers located -10, -20, and -30 kb upstream of the gene promoter, occupied by activated VDR and prebound C/EBPβ and RUNX2, respectively. Initially, bacterial artificial chromosome clone recombineering and traditional mutagenesis defined binding sites for VDR and RUNX2. We then employed a CRISPR/Cas9 gene editing approach to delete the -10 and -30 kb Mmp13 enhancers, a region proximal to the promoter, and VDR or RUNX2. VDR-mediated up-regulation of Mmp13 transcription was completely abrogated upon removal of the -10 kb enhancer, resulting in a 1,25(OH)2D3-directed repression of Mmp13. Deletion of either the -30 kb enhancer or RUNX2 resulted in a complete loss of basal transcript activity and a ChIP-identified destabilization of the chromatin enhancer environment and factor binding. Whereas enhancer deletions only affected Mmp13 expression, the RUNX2 deletion led to changes in gene expression, a reduction in cellular proliferation, and an inability to differentiate. We conclude that the Mmp13 gene is regulated via at least three specific distal enhancers that display independent activities yet are able to integrate response from multiple signaling pathways in a model of activation and suppression.
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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.