Nuclear myosin 1c facilitates the chromatin modifications required to activate rRNA gene transcription and cell cycle progression

PLoS Genet. 2013 Mar;9(3):e1003397. doi: 10.1371/journal.pgen.1003397. Epub 2013 Mar 21.

Abstract

Actin and nuclear myosin 1c (NM1) cooperate in RNA polymerase I (pol I) transcription. NM1 is also part of a multiprotein assembly, B-WICH, which is involved in transcription. This assembly contains the chromatin remodeling complex WICH with its subunits WSTF and SNF2h. We report here that NM1 binds SNF2h with enhanced affinity upon impairment of the actin-binding function. ChIP analysis revealed that NM1, SNF2h, and actin gene occupancies are cell cycle-dependent and require intact motor function. At the onset of cell division, when transcription is temporarily blocked, B-WICH is disassembled due to WSTF phosphorylation, to be reassembled on the active gene at exit from mitosis. NM1 gene knockdown and motor function inhibition, or stable expression of NM1 mutants that do not interact with actin or chromatin, overall repressed rRNA synthesis by stalling pol I at the gene promoter, led to chromatin alterations by changing the state of H3K9 acetylation at gene promoter, and delayed cell cycle progression. These results suggest a unique structural role for NM1 in which the interaction with SNF2h stabilizes B-WICH at the gene promoter and facilitates recruitment of the HAT PCAF. This leads to a permissive chromatin structure required for transcription activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Actins* / genetics
  • Actins* / metabolism
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Cell Cycle Checkpoints*
  • Cell Nucleus / metabolism
  • Chromatin Assembly and Disassembly / genetics*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Histone-Lysine N-Methyltransferase / metabolism
  • Humans
  • Myosin Type I* / genetics
  • Myosin Type I* / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Polymerase I / metabolism
  • RNA, Ribosomal* / genetics
  • RNA, Ribosomal* / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Actins
  • BAZ1B protein, human
  • Chromosomal Proteins, Non-Histone
  • RNA, Ribosomal
  • Transcription Factors
  • Histone-Lysine N-Methyltransferase
  • RNA Polymerase I
  • Adenosine Triphosphatases
  • Myosin Type I
  • SMARCA5 protein, human
  • MYO1C protein, human

Grants and funding

This work was supported by grants from the Swedish Research Council (Vetenskapsrådet) and the Swedish Cancer Society (Cancerfonden) to PP and A-KÖ. EL was a recipient of postdoctoral fellowships from FEBS, Fondation pour la Recherche Médicale (FRM), and Wenner-Gren Foundation, currently funded by the Japanese Society for the Promotion of Science (JSPS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.