Abstract
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.
Highlights
Lamins (A/C and B) are major constituents of the nuclear lamina (NL)
In combination with whole-genome chromatin conformation capture (Hi-C), we demonstrated that euchromatin lamin B1-associated domains (eLADs) are located in the active (A) compartment and that, at the onset of epithelial-to-mesenchymal transition (EMT), the amount of lamin B1 increased at topologically associating domain (TAD) borders concomitantly with increased border strength
Lamin B1 associates with euchromatin regions that are dynamic during EMT
Summary
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. Recent ChIP-seq genome-wide studies have shown that lamin A/C contact euchromatin[18,19] and have suggested a functional role for lamin A/C in creating a permissive environment for gene regulation[18] These findings are of high interest for two main reasons: (1) they demonstrate interactions between large euchromatin regions and nucleoplasmic lamin A; and (2) methodologically, they show how enrichment of different chromatin fractions can reveal distinct lamin A-associated domains[20]. DamID maps of lamin A and B are similar, a fraction of lamin A is found throughout the nucleus that is not detected by DamID, for yet unknown reasons[11,21] This fact, together with evidence that lamins form separate but interconnected networks[12,13] and interact with nuclear structures distinct from the NL6,16,17, led us to hypothesize that lamin B1 filaments could interact with euchromatin. Depletion of lamin B1 from the euchromatin fraction massively affected the gene expression profile (as determined by RNA-seq) at a key time point of this cellular transformation, resulting in impaired EMT
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
