Nuclear lamins are major components of the nuclear lamina, a proteinaceous scaffold structure at the interface between chromatin and the inner nuclear membrane. The nuclear lamina was proposed to mechanically support the nuclear envelope and to provide anchorage sites for heterochromatin, thereby contributing to gene silencing. Roland Foisner’s group has been focusing on a different, up to now poorly investigated mobile pool of A-type lamins that localizes and diffuses throughout the entire nucleus.
Most previous studies have shown that lamins exclusively bind to heterochromatin at the nuclear envelope and further stabilize repression of genes. Kevin Gesson in Roland Foisner’s team in collaboration with bioinformaticians Philipp Rescheneder and Arndt von Haeseler found that in addition to the previously described interaction of lamins with heterochromatin, the mobile pool of lamins in the nucleoplasm also binds to euchromatin. Depletion of the nucleoplasmic lamin pool by knocking out a protein stabilizing nucleoplasmic lamins (called lamin-associated polypeptide 2alpha, in short LAP2alpha) led to a profound reorganization of lamin-chromatin interactions and to changes in the epigenetic profile in euchromatin. Based on these findings they propose that LAP2alpha together with lamins in the nuclear interior regulate chromatin organization, compaction and accessibility. Their results also indicate that lamins serve different functions in euchromatin versus heterochromatin.
The findings of the study not only indicate a new role of lamins in genome organization, they also open new avenues for unraveling novel disease mechanisms and potential therapies in rare diseases caused by mutations in the lamin gene such as the premature aging disease progeria. In line with these findings, the Foisner group has recently shown that expression of LAP2alpha in progeria cells can rescue some of the cellular disease phenotypes (Read more: When 8-year olds look like 80: Viennese researchers describe mechanism behind premature aging disease).
Publication in Genome Research:
Kevin Gesson, Philipp Rescheneder, Michael P. Skoruppa, Arndt von Haeseler, Thomas Dechat and Roland Foisner: A-type lamins bind both hetero- and euchromatin, the latter being regulated by lamina-associated polypeptide 2alpha. In: Genome Research (January 2016).