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.

Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes / E. Cesarini, C. Mozzetta, F. Marullo, F. Gregoretti, A. Gargiulo, M. Columbaro, A. Cortesi, L. Antonelli, S. Di Pelino, S. Squarzoni, D. Palacios, A. Zippo, B. Bodega, G. Oliva, C. Lanzuolo. - In: THE JOURNAL OF CELL BIOLOGY. - ISSN 0021-9525. - 211:3(2015), pp. 533-551. [10.1083/jcb.201504035]

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

B. Bodega;
2015

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.
Animals; Cell Differentiation; Cell Line; Cell Nucleus; Chromatin; Drosophila; Epigenesis, Genetic; Humans; Lamin Type A; Mice; Mice, Inbred C57BL; Nuclear Envelope; Polycomb-Group Proteins; Transcription, Genetic
Settore BIO/11 - Biologia Molecolare
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/825333
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