title: Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes.
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.
authors.affiliation: Consiglio Nazionale delle Ricerche Institute of Cellular Biology and Neurobiology, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, 00143 Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cesarini
authors.affiliation: Consiglio Nazionale delle Ricerche Institute of Cellular Biology and Neurobiology, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, 00143 Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mozzetta
authors.affiliation: Consiglio Nazionale delle Ricerche Institute of Cellular Biology and Neurobiology, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, 00143 Rome, Italy.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Marullo
authors.affiliation: Consiglio Nazionale delle Ricerche Institute for High Performance Computing and Networking, 80131 Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gregoretti
authors.affiliation: Consiglio Nazionale delle Ricerche Institute of Cellular Biology and Neurobiology, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, 00143 Rome, Italy.
authors.forename: Annagiusi
authors.initials: A
authors.lastname: Gargiulo
authors.affiliation: Struttura Complessa Laboratorio Biologia Cellulare Muscoloscheletrica, Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Columbaro
authors.affiliation: Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Cortesi
authors.affiliation: Consiglio Nazionale delle Ricerche Institute for High Performance Computing and Networking, 80131 Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Antonelli
authors.affiliation: Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Di Pelino
authors.affiliation: Struttura Complessa Laboratorio Biologia Cellulare Muscoloscheletrica, Istituto Ortopedico Rizzoli, 40136 Bologna, Italy Consiglio Nazionale delle Ricerche Institute of Molecular Genetics, 40136 Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Squarzoni
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, 00143 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Palacios
authors.affiliation: Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Zippo
authors.affiliation: Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bodega
authors.affiliation: Consiglio Nazionale delle Ricerche Institute for High Performance Computing and Networking, 80131 Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Oliva
authors.affiliation: 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.
authors.forename: Chiara
authors.initials: C
authors.lastname: Lanzuolo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D004330:Drosophila; D044127:Epigenesis, Genetic / Q000235:genetics; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D002843:Chromatin; D034904:Lamin Type A; D063146:Polycomb-Group Proteins; C440308:lamin C