AI Article Synopsis
- LADs (lamina-associated domains) play a crucial role in stabilizing the genome and influence gene expression during the differentiation of adipose stem cells into adipocytes.
- Changes in the positioning of LADs during the first 72 hours of differentiation were observed, with certain adipogenic genes being released from LADs while non-adipogenic genes were retained.
- The study suggests that while LADs contribute to the organization and repression of genes not relevant for adipose tissue, their repositioning does not fully align with the changes in gene expression, indicating a complex relationship during adipogenesis.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996409 | PMC |
| http://dx.doi.org/10.1186/s13059-022-02662-6 | DOI Listing |
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