TY - JOUR
T1 - In β-actin knockouts, epigenetic reprogramming and rDNA transcription inactivation lead to growth and proliferation defects
AU - Almuzzaini, Bader
AU - Sarshad, Aishe A.
AU - Rahmanto, Aldwin S.
AU - Hansson, Magnus L.
AU - Von Euler, Anne
AU - Sangfelt, Olle
AU - Visa, Neus
AU - Farrants, Ann Kristin Östlund
AU - Percipalle, Piergiorgio
N1 - Publisher Copyright:
© 2016 FASEB.
PY - 2016/8
Y1 - 2016/8
N2 - 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.
AB - 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.
KW - Genome-wide analysis
KW - NM1
KW - Nuclear actin
KW - RRNA synthesis
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UR - http://www.scopus.com/inward/citedby.url?scp=84982710701&partnerID=8YFLogxK
U2 - 10.1096/fj.201600280R
DO - 10.1096/fj.201600280R
M3 - Article
C2 - 27127100
AN - SCOPUS:84982710701
SN - 0892-6638
VL - 30
SP - 2860
EP - 2873
JO - FASEB Journal
JF - FASEB Journal
IS - 8
ER -