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In beta-actin knockouts, epigenetic reprogramming and rDNA transcription inactivation lead to growth and proliferation defects
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Number of Authors: 9
2016 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 30, no 8, 2860-2873 p.Article in journal (Refereed) Published
Abstract [en]

Actin and nuclear myosin 1 (NM1) are regulators of transcription and chromatin organization. Using a genome-wide approach, we report here that beta-actin binds intergenic and genic regions across the mammalian genome, associated with both protein-coding and rRNA genes. Within the rDNA, the distribution of beta-actin correlated with NM1 and the other subunits of the B-WICH complex, WSTF and SNF2h. In beta-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 beta-actin, in contrast to mutated forms with polymerization defects, efficiently rescued rRNA synthesis underscoring the direct role for a polymerization-competent form of beta-actin in Pol I transcription. The rRNA synthesis defects in the beta-actin(-/-) MEFs are a consequence of epigenetic reprogramming with up-regulation of the repressive mark H3K4me1 (mono-methylation 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 beta-actin synergizes with NM1 to coordinate permissive chromatin with Pol I transcription, cell growth, and proliferation.

Place, publisher, year, edition, pages
2016. Vol. 30, no 8, 2860-2873 p.
Keyword [en]
genome-wide analysis, NM1, nuclear actin, rRNA synthesis
National Category
Biological Sciences
URN: urn:nbn:se:su:diva-134463DOI: 10.1096/fj.201600280RISI: 000380994000021PubMedID: 27127100OAI: diva2:1033381
Available from: 2016-10-06 Created: 2016-10-06 Last updated: 2016-10-06Bibliographically approved

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Von Euler, AnneVisa, NeusÖstlund Farrants, Ann-KristinPercipalle, Piergiorgio
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Department of Molecular Biosciences, The Wenner-Gren Institute
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