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Effects of Lamina-Chromatin Attachment on Super Long-Range Chromatin Interactions

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Journal bioRxiv
Date 2025 Mar 3
PMID 40027763
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Abstract

The interactions between chromatin and lamin proteins localized on the nuclear envelope play a crucial role in the three-dimensional (3D) organization of the genome. This study investigates the influence of lamin associated domains (LADs) on genome organization at the chromosome level using 3D polymer models of mouse embryonic fibroblasts (MEFs) and embryonic stem cells (mESCs). By integrating genome-wide LAD maps from DamID assays, we simulated chromatin conformations with and without LAD attachment to the nuclear envelope. Our results show that incorporating LAD-lamin interactions yields a radial chromatin distribution consistent with experimental observations. Moreover, LAD-lamin interactions induce significant super long-range chromatin contacts across distant genomic regions. These findings suggest two distinct mechanisms driving induction of chromatin interactions by LAD-lamin attachment.

References
1.
Tolokh I, Kinney N, Sharakhov I, Onufriev A . Strong interactions between highly dynamic lamina-associated domains and the nuclear envelope stabilize the 3D architecture of Drosophila interphase chromatin. Epigenetics Chromatin. 2023; 16(1):21. PMC: 10228000. DOI: 10.1186/s13072-023-00492-9. View

2.
Contessoto V, Cheng R, Onuchic J . Uncovering the statistical physics of 3D chromosomal organization using data-driven modeling. Curr Opin Struct Biol. 2022; 75:102418. DOI: 10.1016/j.sbi.2022.102418. View

3.
Gursoy G, Xu Y, Kenter A, Liang J . Spatial confinement is a major determinant of the folding landscape of human chromosomes. Nucleic Acids Res. 2014; 42(13):8223-30. PMC: 4117743. DOI: 10.1093/nar/gku462. View

4.
van Steensel B, Henikoff S . Identification of in vivo DNA targets of chromatin proteins using tethered dam methyltransferase. Nat Biotechnol. 2000; 18(4):424-8. DOI: 10.1038/74487. View

5.
Chiang M, Michieletto D, Brackley C, Rattanavirotkul N, Mohammed H, Marenduzzo D . Polymer Modeling Predicts Chromosome Reorganization in Senescence. Cell Rep. 2019; 28(12):3212-3223.e6. PMC: 6859504. DOI: 10.1016/j.celrep.2019.08.045. View