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.
No
English
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
Articolo
Esperti anonimi
Pubblicazione scientifica
2015
Rockefeller University Press
211
3
533
551
19
Pubblicato
Periodico con rilevanza internazionale
Aderisco
info:eu-repo/semantics/article
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]
open
Prodotti della ricerca::01 - Articolo su periodico
15
262
Article (author)
no
E. Cesarini, C. Mozzetta, F. Marullo, F. Gregoretti, A. Gargiulo, M. Columbaro, A. Cortesi, L. Antonelli, S. Di Pelino, S. Squarzoni, D. Palacios, A. ...espandi
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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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