The nuclear membrane protein Samp1 links peripheral genome organization to the myogenic transcriptional program

Samp1 is a protein found in the inner nuclear membrane that plays a crucial role in myogenic differentiation and chromatin organization at the nuclear periphery. Researchers studied the connection between these functions by examining the effects of Samp1 depletion during C2C12 myogenic differentiation. This was done through various techniques, including immunofluorescence microscopy, RNA sequencing, FRIC, and chromosome-positioning analysis.

Cells lacking Samp1 displayed significantly reduced MyHC expression and failed to form multinucleated fibers. While cell-cycle withdrawal was not prevented, the transcriptional program responsible for differentiation was severely disrupted. This led to a decrease in muscle-associated transcripts and incomplete repression of genes typically downregulated during myogenesis.

The study also revealed that Samp1 depletion disrupted peripheral chromatin organization and prevented the accumulation of peripheral heterochromatin typically observed during differentiation. Additionally, radial chromosome distribution was compromised, as chromosome 8 failed to reposition to the nuclear periphery during differentiation. In summary, these findings establish a link between Samp1's role in myogenic differentiation and its involvement in genome organization at the nuclear periphery.