title: In β-actin knockouts, epigenetic reprogramming and rDNA transcription inactivation lead to growth and proliferation defects.
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.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden; and.
authors.forename: Bader
authors.initials: B
authors.lastname: Almuzzaini
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden;
authors.forename: Aishe A
authors.initials: AA
authors.lastname: Sarshad
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden;
authors.forename: Aldwin S
authors.initials: AS
authors.lastname: Rahmanto
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden;
authors.forename: Magnus L
authors.initials: ML
authors.lastname: Hansson
authors.affiliation: King Abdullah International Medical Research Center, National Guard Health Affairs, Riyadh, Saudi Arabia.
authors.forename: Anne
authors.initials: A
authors.lastname: Von Euler
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden;
authors.forename: Olle
authors.initials: O
authors.lastname: Sangfelt
authors.affiliation: King Abdullah International Medical Research Center, National Guard Health Affairs, Riyadh, Saudi Arabia.
authors.forename: Neus
authors.initials: N
authors.lastname: Visa
authors.affiliation: King Abdullah International Medical Research Center, National Guard Health Affairs, Riyadh, Saudi Arabia.
authors.forename: Ann-Kristin Östlund
authors.initials: AK
authors.lastname: Farrants
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden; King Abdullah International Medical Research Center, National Guard Health Affairs, Riyadh, Saudi Arabia Division of Science, Department of Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates pp69@nyu.edu.
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Percipalle
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000502:physiology*; D002843:Chromatin; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D024461:Myosin Type I / Q000235:genetics / Q000378:metabolism; D035463:Pol1 Transcription Initiation Complex Proteins / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D000199:Actins; D002843:Chromatin; D004275:DNA, Ribosomal; C470422:Myo1c protein, mouse; D035463:Pol1 Transcription Initiation Complex Proteins; D024461:Myosin Type I
keywords: NM1; genome-wide analysis; nuclear actin; rRNA synthesis