ArticleDevelopmental cell2018
Combinatorial CRISPR/Cas9 Approach to Elucidate a Far-Upstream Enhancer Complex for Tissue-Specific Sox9 Expression.
Article in Developmental cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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
33 citing papers in PubMed, 51 citations in OpenAlex.
- Meckel's cartilage and SOX9/Scx expression during morphogenesis of the mouse mylohyoid attachment site.Anatomical science international · 2026Article
- Techniques to detect physical interactions between genomic regions.Epigenomics · 2025Review
- SOX9: a novel janus-faced regulator in immunity and its promise as a therapeutic target.Frontiers in molecular biosciences · 2025Review
- Molecular basis of individual locomotor function: Integrated understanding of gene expression regulation in the development and homeostasis of the musculoskeletal system.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- iPSCs chondrogenic differentiation for personalized regenerative medicine: a literature review.Stem cell research & therapy · 2024Review
- Chromatin profiling identifies chondrocyte-specific Sox9 enhancers important for skeletal development.JCI insight · 2024Article
- Skeletal growth is enhanced by a shared role for SOX8 and SOX9 in promoting reserve chondrocyte commitment to columnar proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Review
- Modern Approaches to Mouse Genome Editing Using the CRISPR-Cas Toolbox and Their Applications in Functional Genomics and Translational Research.Advances in experimental medicine and biology · 2023Review
- CRISPR/Cas9 system: a reliable and facile genome editing tool in modern biology.Molecular biology reports · 2022Review
- COX7A2L genetic variants determine cardiorespiratory fitness in mice and human.Nature metabolism · 2022Article
- SOX9 in organogenesis: shared and unique transcriptional functions.Cellular and molecular life sciences : CMLS · 2022Review
- A Ctnnb1 enhancer regulates neocortical neurogenesis by controlling the abundance of intermediate progenitors.Cell discovery · 2022Article
- Cartilage Homeostasis and Osteoarthritis.International journal of molecular sciences · 2022Review
- Genome-scale actions of master regulators directing skeletal development.The Japanese dental science review · 2021Review
- Article
- Enhancing CRISPR deletion via pharmacological delay of DNA-PKcs.Genome research · 2021Article
- Epigenome engineering: new technologies for precision medicine.Nucleic acids research · 2020Article
- Mass spectrometry-based proteomic capture of proteins bound to the MACC1 promoter in colon cancer.Clinical & experimental metastasis · 2020Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
SRY-box 9 (SOX9) is a master transcription factor that regulates cartilage development. SOX9 haploinsufficiency resulting from breakpoints in a ∼1-Mb region upstream of SOX9 was reported in acampomelic campomelic dysplasia (ACD) patients, suggesting that essential enhancer regions of SOX9 for cartilage development are located in this long non-coding sequence. However, the cis-acting enhancer region regulating cartilage-specific SOX9 expression remains to be identified. To identify distant cartilage Sox9 enhancers, we utilized the combination of multiple CRISPR/Cas9 technologies including enrichment of the promoter-enhancer complex followed by next-generation sequencing and mass spectrometry (MS), SIN3A-dCas9-mediated epigenetic silencing, and generation of enhancer deletion mice. As a result, we could identify a critical far-upstream cis-element and Stat3 as a trans-acting factor, regulating cartilage-specific Sox9 expression and subsequent skeletal development. Our strategy could facilitate definitive ACD diagnosis and should be useful to reveal the detailed chromatin conformation and regulation.
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Registered trials
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.