%0 Journal Article
%T Interplay of lamin A and lamin B LADs on the radial positioning of chromatin
%A Anna£¿l Brunet
%A Frida Forsberg
%A Philippe Collas
%A Tharvesh M. Liyakat Ali
%J Archive of "Nucleus".
%D 2019
%R 10.1080/19491034.2019.1570810
%X Immunosuppressive drugs such as cyclosporin A (CsA) can elicit hepatotoxicity by affecting gene expression. Here, we address the link between CsA and large-scale chromatin organization in HepG2 hepatocarcinoma cells. We show the existence of lamina-associated domains (LADs) interacting with lamin A, lamin B, or both. These ¡®A-B¡¯, ¡®A-only¡¯ and ¡®B-only¡¯ LADs display distinct fates after CsA treatment: A-B LADs remain constitutive or lose A, A-only LADs mainly lose A or switch to B, and B-only LADs remain B-only or acquire A. LAD rearrangement is overall uncoupled from changes in gene expression. Three-dimensional (3D) genome modeling predicts changes in radial positioning of LADs as LADs switch identities, which are corroborated by fluorescence in situ hybridization. Our results reveal interplay between A- and B-type lamins on radial locus positioning, suggesting complementary contributions to large-scale genome architecture. The data also unveil a hitherto unsuspected impact of cytotoxic drugs on genome conformation.Abbreviations: ChIP-seq: chromatin immunoprecipitation sequencing; CsA: cyclosporin A; FISH; fluorescence in situ hybridization; ICMT: isoprenylcysteine methyltransferase; LAD: lamina-associated domain; TAD: topologically-associated domai
%K Chromatin
%K LAD
%K nuclear lamins
%K genome conformation
%K 3D genome
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363278/