Autosomal dominantly inherited missense mutations in lamins A and C cause several tissue-specific diseases, including Emery-Dreifuss muscular dystrophy (EDMD) and Dunnigan-type familial partial lipodystrophy (FPLD).Here we analyze myoblast-to-myotube differentiation in C2C12 clones overexpressing lamin A mutated at arginine 453 (R453W), one of the most frequent mutations in EDMD. In contrast with clones expressing wild-type lamin A, these clones differentiate poorly or not at all, do not exit the cell cycle properly, and are extensively committed to apoptosis. These disorders are correlated with low levels of expression of transcription factor myogenin and with the persistence of a large pool of hyperphosphorylated retinoblastoma protein. Since clones mutated at arginine 482 (a site responsible for FPLD) differentiate normally, we conclude that C2C12 clones expressing R453W-mutated lamin A represent a good cellular model to study the pathophysiology of EDMD. Our hypothesis is that lamin A mutated at arginine 453 fails to build a functional scaffold and/or to maintain the chromatin compartmentation required for differentiation of myoblasts into myocytes.Lamins A and C are nuclear intermediate filament proteins that are expressed in nearly all somatic cells. Mutations in these proteins cause diseases that affect striated muscle, adipose tissue, peripheral nerves, or skeletal development (56). Hutchinson-Gilford progeria syndrome, a form of accelerated aging in childhood, has been recently shown to be due to mutations in lamin A (13, 16). Three muscular diseases, EmeryDreifuss muscular dystrophy (EDMD), dilated cardiomyopathy with conduction defect 1, and limb girdle muscular dystrophy type 1B, are dominant. Mice lacking A-type lamins or deficient in prelamin A maturation develop skeletal and cardiac lethal muscular dystrophies soon after birth, confirming the importance of A-type lamins for muscle differentiation and/or maintenance (43, 51). However, the mechanisms by which mutations in these ubiquitous proteins generate tissuespecific diseases are presently unknown.In all metazoan nuclei, lamins form a meshwork (named the nuclear lamina) located between the inner nuclear membrane and chromatin (50). Lamins interact with both integral proteins of this membrane and DNA and chromatin proteins (49, 55). Two types of lamins are present in somatic cells of vertebrates. A-type lamins (lamin A, lamin C, and lamin ⌬10) are somatic cell isoforms arising by alternative splicing from the LMNA gene located on chromosome 1q21.2 (21,29,30,35,57). Lamin A and lamin C are identical over their first 566 amino acids. A-type lamins are not expressed in early embryos or in adult stem cells and become progressively expressed during development and cell differentiation (50). B-type lamins (B1 and B2) that are encoded by different genes are constitutively expressed in all cell types (2). Like all intermediate filament proteins, lamins have a conserved central ␣-helical domain that is responsible for the formation of coiled-coil dimers f...

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BackgroundThe importance of transposable elements (TEs) in the genomic remodeling and chromosomal rearrangements that accompany lineage diversification in vertebrates remains the subject of debate. The major impediment to understanding the roles of TEs in genome evolution is the lack of comparative and integrative analyses on complete taxonomic groups. To help overcome this problem, we have focused on the Antarctic teleost genus Trematomus (Notothenioidei: Nototheniidae), as they experienced rapid speciation accompanied by dramatic chromosomal diversity. Here we apply a multi-strategy approach to determine the role of large-scale TE mobilization in chromosomal diversification within Trematomus species.ResultsDespite the extensive chromosomal rearrangements observed in Trematomus species, our measurements revealed strong interspecific genome size conservation. After identifying the DIRS1, Gypsy and Copia retrotransposon superfamilies in genomes of 13 nototheniid species, we evaluated their diversity, abundance (copy numbers) and chromosomal distribution. Four families of DIRS1, nine of Gypsy, and two of Copia were highly conserved in these genomes; DIRS1 being the most represented within Trematomus genomes. Fluorescence in situ hybridization mapping showed preferential accumulation of DIRS1 in centromeric and pericentromeric regions, both in Trematomus and other nototheniid species, but not in outgroups: species of the Sub-Antarctic notothenioid families Bovichtidae and Eleginopsidae, and the non-notothenioid family Percidae.ConclusionsIn contrast to the outgroups, High-Antarctic notothenioid species, including the genus Trematomus, were subjected to strong environmental stresses involving repeated bouts of warming above the freezing point of seawater and cooling to sub-zero temperatures on the Antarctic continental shelf during the past 40 millions of years (My). As a consequence of these repetitive environmental changes, including thermal shocks; a breakdown of epigenetic regulation that normally represses TE activity may have led to sequential waves of TE activation within their genomes. The predominance of DIRS1 in Trematomus species, their transposition mechanism, and their strategic location in “hot spots” of insertion on chromosomes are likely to have facilitated nonhomologous recombination, thereby increasing genomic rearrangements. The resulting centric and tandem fusions and fissions would favor the rapid lineage diversification, characteristic of the nototheniid adaptive radiation.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4714-x) contains supplementary material, which is available to authorized users.