Interplay of the nuclear envelope with chromatin in physiology and pathology

Nucleus. 2020 Dec;11(1):205-218. doi: 10.1080/19491034.2020.1806661.

Abstract

The nuclear envelope compartmentalizes chromatin in eukaryotic cells. The main nuclear envelope components are lamins that associate with a panoply of factors, including the LEM domain proteins. The nuclear envelope of mammalian cells opens up during cell division. It is reassembled and associated with chromatin at the end of mitosis when telomeres tether to the nuclear periphery. Lamins, LEM domain proteins, and DNA binding factors, as BAF, contribute to the reorganization of chromatin. In this context, an emerging role is that of the ESCRT complex, a machinery operating in multiple membrane assembly pathways, including nuclear envelope reformation. Research in this area is unraveling how, mechanistically, ESCRTs link to nuclear envelope associated factors as LEM domain proteins. Importantly, ESCRTs work also during interphase for repairing nuclear envelope ruptures. Altogether the advances in this field are giving new clues for the interpretation of diseases implicating nuclear envelope fragility, as laminopathies and cancer.

Abbreviations: na, not analyzed; ko, knockout; kd, knockdown; NE, nuclear envelope; LEM, LAP2-emerin-MAN1 (LEM)-domain containing proteins; LINC, linker of nucleoskeleton and cytoskeleton complexes; Cyt, cytoplasm; Chr, chromatin; MB, midbody; End, endosomes; Tel, telomeres; INM, inner nuclear membrane; NP, nucleoplasm; NPC, Nuclear Pore Complex; ER, Endoplasmic Reticulum; SPB, spindle pole body.

Keywords: Chromatin; ESCRT; cancer; genome rearrangements; midbody; nuclear envelope; telomeres.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Video-Audio Media

MeSH terms

  • Animals
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin / pathology
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • Humans
  • Interphase
  • Laminopathies / genetics
  • Laminopathies / metabolism*
  • Laminopathies / pathology
  • Lamins / genetics
  • Lamins / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism*
  • Nuclear Envelope / pathology

Substances

  • Chromatin
  • Endosomal Sorting Complexes Required for Transport
  • Lamins
  • Neoplasm Proteins

Grants and funding

This work was supported by the Fondazione Italiana per la Ricerca sul Cancro [22392]; Sapienza Università di Roma [AR21916B6FF63463]; Sapienza Università di Roma [RP11916B7F20A9E3]; Progeria Research Foundation USA.