ArticleCell cycle (Georgetown, Tex.)2015
De-regulated expression of the BRG1 chromatin remodeling factor in bone marrow mesenchymal stromal cells induces senescence associated with the silencing of NANOG and changes in the levels of chromatin proteins.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Epigenetic roles of chromatin remodeling complexes in bone biology and the pathogenesis of bone‑related disease (Review).International journal of molecular medicine · 2025Review
- Craniomaxillofacial-Derived MSCs in Congenital Defect Reconstruction.Biomolecules · 2025Review
- Characterization of senescent mesenchymal stem/stromal cells derived from equine bone marrow and the effects of NANOG on the senescent phenotypes.The Journal of veterinary medical science · 2024Article
- Regulation Mechanisms and Maintenance Strategies of Stemness in Mesenchymal Stem Cells.Stem cell reviews and reports · 2024Review
- Epigenetic regulation of mesenchymal stem cell aging through histone modifications.Genes & diseases · 2023Review
- Impact of Environmental and Epigenetic Changes on Mesenchymal Stem Cells during Aging.International journal of molecular sciences · 2023Review
- Molecular Crosstalk between Chromatin Remodeling and Tumor Microenvironment in Multiple Myeloma.Current oncology (Toronto, Ont.) · 2022Review
- Mesenchymal Stem/Stromal Cell Senescence: Hallmarks, Mechanisms, and Combating Strategies.Stem cells translational medicine · 2022Review
- The Mechanism of Stem Cell Aging.Stem cell reviews and reports · 2022Review
- Cyclic DNA remethylation following active demethylation at euchromatic regions in mouse embryonic stem cells.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2021Article
- ATP-dependent chromatin remodelers in ageing and age-related disorders.Biogerontology · 2021Review
- Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging.Biomolecules · 2020Review
- Heat Shock Alters Mesenchymal Stem Cell Identity and Induces Premature Senescence.Frontiers in cell and developmental biology · 2020Article
- ATP-Dependent Chromatin Remodeling Complex in the Lineage Specification of Mesenchymal Stem Cells.Stem cells international · 2020Review
- Epigenetic Regulation in Mesenchymal Stem Cell Aging and Differentiation and Osteoporosis.Stem cells international · 2020Review
- Senescence in Mesenchymal Stem Cells: Functional Alterations, Molecular Mechanisms, and Rejuvenation Strategies.Frontiers in cell and developmental biology · 2020Review
- Senescence Phenomena and Metabolic Alteration in Mesenchymal Stromal Cells from a Mouse Model of Rett Syndrome.International journal of molecular sciences · 2019Article
- Epigenetic regulation in cell senescence.Journal of molecular medicine (Berlin, Germany) · 2017Review
- SMARCD1 regulates senescence-associated lipid accumulation in hepatocytes.NPJ aging and mechanisms of disease · 2017Article
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stem cells have a peculiar chromatin architecture that contributes to their unique properties, including uncommitted status, multi/pluripotency and self-renewal. We analyzed the effect of the de-regulation of the SWI/SNF chromatin remodeling complex in mesenchymal stromal cells (MSC) through the silencing and up-regulation of BRG1, which is the ATPase subunit of the complex. The altered expression of BRG1 promoted the senescence of MSC with suppression of the NANOG transcription, which is part of the transcriptional circuitry governing stem cell functions. To gain insight on the way NANOG was silenced, we evaluated how the de-regulated BRG1 expression affect the binding of activators and repressors on the NANOG promoter. We found 4 E2F binding motifs on NANOG promoter, which can be occupied by RB1 and RB2/P130. These are members of the retinoblastoma gene family. In MSC with a silenced BRG1, the relative binding of the 2 retinoblastoma proteins increased, and this was associated with the recruitment of DNMT1. This induced the methylation of CpG on the NANOG promoter. Opposingly, when a high level of BRG1 was present, the same E2F binding motifs were docking sites for BRG1, which induced chromatin compaction without CpG methylation but with increased histone deacetylation, associated with the presence of HDAC1 on E2F binding sites. Besides the sharp regulation of the NANOG expression, we evidenced, through proteomic analysis, that the de-regulation of the SWI/SNF function affected the expression of histones and other nuclear proteins involved in "nuclear architecture," suggesting that BRG1 may act as global regulator of gene expression.
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