Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• The FASEB journal, 2016-08, Vol.30 (8), p.2860-2873

Ort / Verlag

United States: Federation of American Societies for Experimental Biology

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 form of β‐actin in Pol I transcription. The rRNA synthesis defects in the β‐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. We propose 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.—Almuzzaini, B., Sarshad, A. A., Rahmanto, A. S., Hansson, M. L., Von Euler, A., Sangfelt, O., Visa, N., Farrants, A.‐K. Ö., Percipalle, P. In β‐actin knockouts, epigenetic reprogramming and rDNA transcription inactivation lead to growth and proliferation defects. FASEB J. 30, 2860‐2873 (2016). www.fasebj.org