Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes

Elisa Cesarini, Chiara Mozzetta, Fabrizia Marullo, Francesco Gregoretti, Annagiusi Gargiulo, Marta Columbaro, Alice Cortesi, Laura Antonelli, Simona Di Pelino, Stefano Squarzoni, Daniela Palacios, Alessio Zippo, Beatrice Bodega, Gennaro Oliva, Chiara Lanzuolo

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Abstract

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.

Original languageEnglish
Pages (from-to)533-551
Number of pages19
JournalJournal of Cell Biology
Volume211
Issue number3
DOIs
Publication statusPublished - Nov 1 2015

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ASJC Scopus subject areas

  • Cell Biology

Cite this

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. Journal of Cell Biology, 211(3), 533-551. https://doi.org/10.1083/jcb.201504035