In β-actin knockouts, epigenetic reprogramming and rDNA transcription inactivation lead to growth and proliferation defects

Bader Almuzzaini, Aishe A. Sarshad, Aldwin S. Rahmanto, Magnus L. Hansson, Anne Von Euler, Olle Sangfelt, Neus Visa, Ann Kristin Östlund Farrants, Piergiorgio Percipalle

Research output: Contribution to journalArticle

Abstract

Actin and nuclear myosin 1 (NM1) are regulators of transcription and chromatin organization. Using a genome-wide approach, we report here that β-actin binds intergenic and genic regions across the mammalian genome, associated with both protein-coding and rRNA genes. Within the rDNA, the distribution of β-actin correlated with NM1 and the other subunits of the B-WICH complex, WSTF and SNF2h. In β-actin-/- mouse embryonic fibroblasts (MEFs), we found that rRNA synthesis levels decreased concomitantly with drops in RNA polymerase I (Pol I) and NM1 occupancies across the rRNA gene. Reintroduction of wild-type β-actin, in contrast to mutated forms with polymerization defects, efficiently rescued rRNA synthesis underscoring the direct role for a polymerization-competent formofβ-actin in Pol I transcription. The rRNA synthesis defects intheβ-actin-/- MEFs are a consequence of epigenetic reprogramming with up-regulation of the repressive mark H3K4me1 (monomethylation of lys4 on histone H3) and enhanced chromatin compaction at promoter-proximal enhancer (T0 sequence), which disturb binding of the transcription factor TTF1. Wepropose a novel genome-wide mechanism where the polymerase-associated β-actin synergizes with NM1 to coordinate permissive chromatin with Pol I transcription, cell growth, and proliferation.

Original languageEnglish (US)
Pages (from-to)2860-2873
Number of pages14
JournalFASEB Journal
Volume30
Issue number8
DOIs
StatePublished - Aug 2016

Keywords

  • Genome-wide analysis
  • NM1
  • Nuclear actin
  • RRNA synthesis

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Almuzzaini, B., Sarshad, A. A., Rahmanto, A. S., Hansson, M. L., Von Euler, A., Sangfelt, O., Visa, N., Farrants, A. K. Ö., & Percipalle, P. (2016). In β-actin knockouts, epigenetic reprogramming and rDNA transcription inactivation lead to growth and proliferation defects. FASEB Journal, 30(8), 2860-2873. https://doi.org/10.1096/fj.201600280R