Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions

J Cell Biol. 2004 Feb 16;164(4):515-26. doi: 10.1083/jcb.200305142.

Abstract

The promyelocytic leukemia (PML) protein is aggregated into nuclear bodies that are associated with diverse nuclear processes. Here, we report that the distance between a locus and its nearest PML body correlates with the transcriptional activity and gene density around the locus. Genes on the active X chromosome are more significantly associated with PML bodies than their silenced homologues on the inactive X chromosome. We also found that a histone-encoding gene cluster, which is transcribed only in S-phase, is more strongly associated with PML bodies in S-phase than in G0/G1 phase of the cell cycle. However, visualization of specific RNA transcripts for several genes showed that PML bodies were not themselves sites of transcription for these genes. Furthermore, knock-down of PML bodies by RNA interference did not preferentially change the expression of genes closely associated with PML bodies. We propose that PML bodies form in nuclear compartments of high transcriptional activity, but they do not directly regulate transcription of genes in these compartments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters
  • Cell Cycle / physiology
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Chromosomes, Human, X
  • Collagen Type I / genetics
  • Collagen Type I, alpha 1 Chain
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Intranuclear Inclusion Bodies / metabolism*
  • Male
  • Multigene Family
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promyelocytic Leukemia Protein
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Regression Analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Tumor Suppressor Proteins

Substances

  • ATP-Binding Cassette Transporters
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Histocompatibility Antigens Class I
  • Neoplasm Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • RNA, Small Interfering
  • Transcription Factors
  • Tumor Suppressor Proteins
  • transporter associated with antigen processing (TAP)
  • PML protein, human