Cesarini, E., Mozzetta, C., Marullo, F., Gregoretti, F., Gargiulo, A., Columbaro, M., Cortesi, A., Antonelli, L., Di Pelino, S., Squarzoni, S., Palacios, D., Zippo, A., Bodega, B., Oliva, G., Lanzuolo, C. (2015). Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes.  J. Cell Biol. 211(3): 533--551.

FBrf0230939

Research paper

Beyond its role in providing structure to the nuclear envelope, lamin A/C is involved in transcriptional regulation. However, its cross talk with epigenetic factors--and how this cross talk influences physiological processes--is still unexplored. Key epigenetic regulators of development and differentiation are the Polycomb group (PcG) of proteins, organized in the nucleus as microscopically visible foci. Here, we show that lamin A/C is evolutionarily required for correct PcG protein nuclear compartmentalization. Confocal microscopy supported by new algorithms for image analysis reveals that lamin A/C knock-down leads to PcG protein foci disassembly and PcG protein dispersion. This causes detachment from chromatin and defects in PcG protein-mediated higher-order structures, thereby leading to impaired PcG protein repressive functions. Using myogenic differentiation as a model, we found that reduced levels of lamin A/C at the onset of differentiation led to an anticipation of the myogenic program because of an alteration of PcG protein-mediated transcriptional repression. Collectively, our results indicate that lamin A/C can modulate transcription through the regulation of PcG protein epigenetic factors.

PMC4639869 (PMC) (EuropePMC)