Local euchromatin enrichment in lamina-associated domains anticipates their repositioning in the adipogenic lineage
Abstract Background Interactions of chromatin with the nuclear lamina via lamina-associated domains (LADs) confer structural stability to the genome. The dynamics of positioning of LADs during differentiation, and how LADs impinge on developmental gene expression, remains, however, elusive. Results...
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Genome Biology |
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| Online Access: | https://doi.org/10.1186/s13059-022-02662-6 |
| _version_ | 1818050977499971584 |
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| author | Julia Madsen-Østerbye Mohamed Abdelhalim Marie-Odile Baudement Philippe Collas |
| author_facet | Julia Madsen-Østerbye Mohamed Abdelhalim Marie-Odile Baudement Philippe Collas |
| author_sort | Julia Madsen-Østerbye |
| collection | DOAJ |
| description | Abstract Background Interactions of chromatin with the nuclear lamina via lamina-associated domains (LADs) confer structural stability to the genome. The dynamics of positioning of LADs during differentiation, and how LADs impinge on developmental gene expression, remains, however, elusive. Results We examined changes in the association of lamin B1 with the genome in the first 72 h of differentiation of adipose stem cells into adipocytes. We demonstrate a repositioning of entire stand-alone LADs and of LAD edges as a prominent nuclear structural feature of early adipogenesis. Whereas adipogenic genes are released from LADs, LADs sequester downregulated or repressed genes irrelevant for the adipose lineage. However, LAD repositioning only partly concurs with gene expression changes. Differentially expressed genes in LADs, including LADs conserved throughout differentiation, reside in local euchromatic and lamin-depleted sub-domains. In these sub-domains, pre-differentiation histone modification profiles correlate with the LAD versus inter-LAD outcome of these genes during adipogenic commitment. Lastly, we link differentially expressed genes in LADs to short-range enhancers which overall co-partition with these genes in LADs versus inter-LADs during differentiation. Conclusions We conclude that LADs are predictable structural features of adipose nuclear architecture that restrain non-adipogenic genes in a repressive environment. |
| first_indexed | 2024-12-10T11:02:03Z |
| format | Article |
| id | doaj.art-3294659d561f4a2697df3787a8de1c62 |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-12-10T11:02:03Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-3294659d561f4a2697df3787a8de1c622022-12-22T01:51:39ZengBMCGenome Biology1474-760X2022-04-0123111910.1186/s13059-022-02662-6Local euchromatin enrichment in lamina-associated domains anticipates their repositioning in the adipogenic lineageJulia Madsen-Østerbye0Mohamed Abdelhalim1Marie-Odile Baudement2Philippe Collas3Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of OsloDepartment of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of OsloDepartment of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of OsloDepartment of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of OsloAbstract Background Interactions of chromatin with the nuclear lamina via lamina-associated domains (LADs) confer structural stability to the genome. The dynamics of positioning of LADs during differentiation, and how LADs impinge on developmental gene expression, remains, however, elusive. Results We examined changes in the association of lamin B1 with the genome in the first 72 h of differentiation of adipose stem cells into adipocytes. We demonstrate a repositioning of entire stand-alone LADs and of LAD edges as a prominent nuclear structural feature of early adipogenesis. Whereas adipogenic genes are released from LADs, LADs sequester downregulated or repressed genes irrelevant for the adipose lineage. However, LAD repositioning only partly concurs with gene expression changes. Differentially expressed genes in LADs, including LADs conserved throughout differentiation, reside in local euchromatic and lamin-depleted sub-domains. In these sub-domains, pre-differentiation histone modification profiles correlate with the LAD versus inter-LAD outcome of these genes during adipogenic commitment. Lastly, we link differentially expressed genes in LADs to short-range enhancers which overall co-partition with these genes in LADs versus inter-LADs during differentiation. Conclusions We conclude that LADs are predictable structural features of adipose nuclear architecture that restrain non-adipogenic genes in a repressive environment.https://doi.org/10.1186/s13059-022-02662-6Adipose stem cellAdipogenesisEnhancerH3K27 acetylationLADLamina-associated domain |
| spellingShingle | Julia Madsen-Østerbye Mohamed Abdelhalim Marie-Odile Baudement Philippe Collas Local euchromatin enrichment in lamina-associated domains anticipates their repositioning in the adipogenic lineage Genome Biology Adipose stem cell Adipogenesis Enhancer H3K27 acetylation LAD Lamina-associated domain |
| title | Local euchromatin enrichment in lamina-associated domains anticipates their repositioning in the adipogenic lineage |
| title_full | Local euchromatin enrichment in lamina-associated domains anticipates their repositioning in the adipogenic lineage |
| title_fullStr | Local euchromatin enrichment in lamina-associated domains anticipates their repositioning in the adipogenic lineage |
| title_full_unstemmed | Local euchromatin enrichment in lamina-associated domains anticipates their repositioning in the adipogenic lineage |
| title_short | Local euchromatin enrichment in lamina-associated domains anticipates their repositioning in the adipogenic lineage |
| title_sort | local euchromatin enrichment in lamina associated domains anticipates their repositioning in the adipogenic lineage |
| topic | Adipose stem cell Adipogenesis Enhancer H3K27 acetylation LAD Lamina-associated domain |
| url | https://doi.org/10.1186/s13059-022-02662-6 |
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