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J Cell Biol. 2015 Nov 9;211(3):533-51. doi: 10.1083/jcb.201504035.

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

Author information

1
Consiglio Nazionale delle Ricerche Institute of Cellular Biology and Neurobiology, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, 00143 Rome, Italy.
2
Consiglio Nazionale delle Ricerche Institute for High Performance Computing and Networking, 80131 Naples, Italy.
3
Struttura Complessa Laboratorio Biologia Cellulare Muscoloscheletrica, Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
4
Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, Italy.
5
Struttura Complessa Laboratorio Biologia Cellulare Muscoloscheletrica, Istituto Ortopedico Rizzoli, 40136 Bologna, Italy Consiglio Nazionale delle Ricerche Institute of Molecular Genetics, 40136 Bologna, Italy.
6
Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, 00143 Rome, Italy.
7
Consiglio Nazionale delle Ricerche Institute of Cellular Biology and Neurobiology, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, 00143 Rome, Italy chiara.lanzuolo@cnr.it.

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.

PMID:
26553927
PMCID:
PMC4639869
DOI:
10.1083/jcb.201504035
[Indexed for MEDLINE]
Free PMC Article

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