CHMP1 is a novel nuclear matrix protein affecting chromatin structure and cell-cycle progression

J Cell Sci. 2001 Jul;114(Pt 13):2383-93. doi: 10.1242/jcs.114.13.2383.

Abstract

The Polycomb-group (PcG) is a diverse set of proteins required for maintenance of gene silencing during development. In a screen for conserved partners of the PcG protein Polycomblike (Pcl), we have identified a new protein, human CHMP1 (CHromatin Modifying Protein; CHarged Multivesicular body Protein), which is encoded by an alternative open reading frame in the PRSM1 gene and is conserved in both complex and simple eukaryotes. CHMP1 contains a predicted bipartite nuclear localization signal and distributes as distinct forms to the cytoplasm and the nuclear matrix in all cell lines tested. We have constructed a stable HEK293 cell line that inducibly overexpresses CHMP1 under ecdysone control. Overexpressed CHMP1 localizes to a punctate subnuclear pattern, encapsulating regions of nuclease-resistant, condensed chromatin. These novel structures are also frequently surrounded by increased histone H3 phosphorylation and acetylation. CHMP1 can recruit a PcG protein, BMI1, to these regions of condensed chromatin and can cooperate with co-expressed vertebrate Pcl in a Xenopus embryo PcG assay; this is consistent with a role in PcG function. In combination, these observations suggest that CHMP1 plays a role in stable gene silencing within the nucleus.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Nuclear
  • Cell Cycle*
  • Chromatin / chemistry*
  • Conserved Sequence
  • Endosomal Sorting Complexes Required for Transport
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / isolation & purification*
  • Nuclear Proteins / physiology
  • Phenotype
  • Vesicular Transport Proteins
  • Xenopus / genetics

Substances

  • Antigens, Nuclear
  • CHMP1A protein, human
  • Chromatin
  • Endosomal Sorting Complexes Required for Transport
  • Nuclear Proteins
  • Vesicular Transport Proteins