The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
The spatial repositioning of adipogenesis genes is correlated with their expression status in a porcine mesenchymal stem cell adipogenesis model system
Abstract
Alterations in the nuclear positioning of chromosomes and specific genes during differentiation and development have suggested strongly the existence of a relationship between non-random organization of the genome and its function. In this study, we have examined the genome organization in interphase nuclei during adipogenesis, using the pig as a model organism. We hypothesized that changes in the gene expression profile and chromatin remodeling which occur during cellular differentiation would elicit repositioning of whole chromosomes, moving specific genes on them to different regions of the nucleus. We established an in vitro adipogenesis differentiation system using mesenchymal stem cells, derived from porcine bone marrow. The nuclear position of seven adipogenesis genes (PPARG, SREBF1, FABP4, CEBPA, CEBPB, CREB, and GATA2), two control genes (SOX9 and MYL1), and six chromosomes carrying these gene loci (SSC4, SSC6, SSC12, SSC13, SSC15, and SSC17) was determined. We found that during adipogenesis, using the in vitro stem cell model system, in contrast to our original hypothesis, the nuclear position of genes involved in adipogenesis was altered radically with the up-regulation of gene expression correlating with these genes becoming more internally located within nuclei. Chromosome territories, containing these genes, were also found to alter their nuclear position during the in vitro adipogenesis model, with the most dramatic repositioning being SSC4 that moved from the nuclear periphery towards the nuclear interior. We found that during in vitro adipogenesis chromosome territories decondensed and the genes were found on loops and projections of chromatin, away from the main body of the chromosomes. From our data, it appears that the temporal repositioning of genes, emanating away from chromosomes, during adipogenesis is correlated with gene activity, supporting models of the involvement of spatial genome repositioning in regulating gene expression and the nuclear interior being an important region of the nucleus for transcription.
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“Lamina-associated domains (LADs), typically located at the nuclear periphery, are enriched in repressive chromatin marks and correlate with low transcriptional activity [74,75].”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [75]
Citations
Cites
Adipocyte differentiation from the inside out
Rosen, E. D., & MacDougald, O. A. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2066 · Cited by 2,607
Transcriptional control of adipocyte formation
Farmer, S. R. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.07.001 · Cited by 1,836
Beyond the Sequence: Cellular Organization of Genome Function
Misteli, T. (2007) · Cell · doi:10.1016/j.cell.2007.01.028 · Cited by 1,140
Active genes dynamically colocalize to shared sites of ongoing transcription
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Differences in the Localization and Morphology of Chromosomes in the Human Nucleus
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Self-citationTranscriptional repression mediated by repositioning of genes to the nuclear lamina
Reddy, K. L., Zullo, J., Bertolino, E., & Singh, H. (2008) · Nature · doi:10.1038/nature06727 · Cited by 823
Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions
Lanctôt, C., Cheutin, T., Cremer, M., Cavalli, G., & Cremer, T. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2041 · Cited by 781
Subnuclear Compartmentalization of Immunoglobulin Loci During Lymphocyte Development
Kosak, S. T., Skok, J. A., Medina, K. L., Riblet, R. J., Beau, M. M. L., Fisher, A. G., & Singh, H. (2002) · Science · doi:10.1126/science.1068768 · Cited by 722
The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells
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Mechanisms and functions of nuclear envelope remodelling
Ungricht, R., & Kutay, U. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.153 · Cited by 353
Harr, J. C., Luperchio, T. R., Wong, X., Cohen, E., Wheelan, S. J., & Reddy, K. L. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201405110 · Cited by 338
Mehta, I. S., Amira, M., Harvey, A., & Bridger, J. M. (2010) · Genome biology · doi:10.1186/gb-2010-11-1-r5 · Cited by 193
Self-citationMechanical Regulation of Nuclear Structure and Function
Martins, R. P., Finan, J. D., Guilak, F., & Lee, D. A. (2012) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071910-124638 · Cited by 151
Genetics of fat tissue accumulation in pigs: a comparative approach
Switonski, M., Stachowiak, M., Cieślak, J., Bartz, M., & Grzes, M. (2010) · Journal of Applied Genetics · doi:10.1007/bf03195724 · Cited by 116
Metadata
- Authors
- Szczerbal, I., Foster, H. A., & Bridger, J. M.
- Affiliations
- Poznań University of Life Sciences (PL)
- Brunel University of London (GB)
- Corresponding author
- Szczerbal, Izabela
- Bridger, Joanna M.
- Venue
- Chromosoma
- Published
- 2009-07-08
- Volume
- 118
- Issue
- 5
- Pages
- 647-663
- ISSN
- 0009-5915 (ISSN-L)
- 1432-0886
- OpenAlex
- W2049017075
- Cited by
- 107
- References
- 73
- Citations by year
- 2025: 4 · 2024: 3 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 9 · 2016: 9 · 2015: 10 · 2014: 15 · 2013: 8 · 2012: 9
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Chromosoma (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brunel University London
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- adipogenesis, chromosome territories, interphase nuclei, mesenchymal stem cells, gene expression regulation, chromatin looping, chromatin decondensation, PPARγ, SREBF1, FABP4, C/EBP, GATA2, SOX9, spatial genome organization
- MeSH terms
- Animals, Cell Differentiation, Genes, Swine, Gene Expression, CCAAT-Enhancer-Binding Proteins, Chromatin Assembly and Disassembly, PPAR gamma, Adipogenesis, GATA2 Transcription Factor, Sterol Regulatory Element Binding Protein 1, Mesenchymal Stem Cells
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