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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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.
Lingua originaleEnglish
pagine (da-a)533-551
Numero di pagine19
RivistaTHE JOURNAL OF CELL BIOLOGY
Volume211
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • Cell Differentiation
  • Cell Nucleus
  • Chromatin
  • Epigenesis, Genetic
  • Lamin Type A
  • Nuclear Envelope
  • Polycomb-Group Proteins
  • Transcription, Genetic

Fingerprint

Entra nei temi di ricerca di 'Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes'. Insieme formano una fingerprint unica.

Cita questo