Lamin B1 mapping reveals the existence of dynamic and functional euchromatin lamin B1 domains

• Published in: Nature communications 2018-08, Vol.9 (1), p.3420-12, Article 3420
• Main Authors: Pascual-Reguant, Laura, Blanco, Enrique, Galan, Silvia, Le Dily, François, Cuartero, Yasmina, Serra-Bardenys, Gemma, Di Carlo, Valerio, Iturbide, Ane, Cebrià-Costa, Joan Pau, Nonell, Lara, de Herreros, Antonio García, Di Croce, Luciano, Marti-Renom, Marc A., Peiró, Sandra
• Format: Article
• Language: English
• Subjects: 45; 45/15; 45/43; 45/77; 45/90; 631/45/147; 631/80/386; 96/63; Animals; Cell Nucleus - metabolism; Chromatin Immunoprecipitation; DNA; Domains; Epithelial-Mesenchymal Transition - genetics; Epithelial-Mesenchymal Transition - physiology; Euchromatin; Euchromatin - chemistry; Euchromatin - genetics; Euchromatin - metabolism; Fluorescence Recovery After Photobleaching; Gene mapping; Genomes; Humanities and Social Sciences; Humans; Lamin Type B - chemistry; Lamin Type B - genetics; Lamin Type B - metabolism; Lamins; Localization; Mapping; Mesenchyme; Mice; multidisciplinary; Nuclear organization; Rodents; Science; Science (multidisciplinary); Transcription
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-05912-z

Lamins (A/C and B) are major constituents of the nuclear lamina (NL). Structurally conserved lamina-associated domains (LADs) are formed by genomic regions that contact the NL. Lamins are also found in the nucleoplasm, with a yet unknown function. Here we map the genome-wide localization of lamin B1 in an euchromatin-enriched fraction of the mouse genome and follow its dynamics during the epithelial-to-mesenchymal transition (EMT). Lamin B1 associates with actively expressed and open euchromatin regions, forming dynamic euchromatin lamin B1-associated domains (eLADs) of about 0.3 Mb. Hi-C data link eLADs to the 3D organization of the mouse genome during EMT and correlate lamin B1 enrichment at topologically associating domain (TAD) borders with increased border strength. Having reduced levels of lamin B1 alters the EMT transcriptional signature and compromises the acquisition of mesenchymal traits. Thus, during EMT, the process of genome reorganization in mouse involves dynamic changes in eLADs. Lamina-associated domains (LADs) contact lamins in the nuclear lamina, and lamin B1 was thought to bind heterochromatic regions at the nuclear envelope. Here, the authors show lamin B1 associates with actively expressed euchromatin regions, creating dynamic euchromatin lamina-associated domains (eLADs) during epithelial-to-mesenchymal transition.