LAP2alpha facilitates myogenic gene expression by preventing spreading of nucleoplasmic lamin A/C to active chromatin regions (RNA-Seq)

A-type lamins form a filamentous meshwork beneath the nuclear membrane that anchors large heterochromatic chromatin domains at the nuclear envelope. They also exist as a more dynamic, non-filamentous pool in the nuclear interior, where they interact with gene-rich euchromatin. Lamin-associated polypeptide 2 alpha (LAP2alpha) binds to and maintains the nucleoplasmic lamin pool, but the functional significance of this interaction is poorly understood. Here we investigate the genome-wide chromatin association of A-type lamins during myogenic differentiation in the presence and absence of LAP2alpha. We find that A-type lamins are significantly reorganized on chromatin upon depletion of LAP2alpha, spreading towards active chromatin and accumulating at regions of active H3K27ac and H3K4me3 histone marks close to the genes whose expression is impaired in the absence of LAP2alpha. This reorganization of A-type lamins on chromatin is accompanied by depletion of the active chromatin mark H3K27ac and a significant delay of myogenic differentiation. Thus, the interplay of lamins and LAP2alpha is crucial for proper positioning of intranuclear lamins on chromatin to allow normal myogenic differentiation. This research was funded in whole or in part by the Austrian Science Fund (FWF) to Roland Foisner: P32512-B/DOI:10.55776/P36503 https://www.doi.org/10.55776/P36503 P36503-B/DOI:10.55776/P32512 https://www.doi.org/10.55776/P32512