In ß-actin knockouts, epigenetic reprogramming and rDNA transcription inactivation lead to growth and proliferation defects.
FASEB J
; 30(8): 2860-73, 2016 08.
Article
en En
| MEDLINE
| ID: mdl-27127100
ABSTRACT
Actin and nuclear myosin 1 (NM1) are regulators of transcription and chromatin organization. Using a genome-wide approach, we report here that ß-actin binds intergenic and genic regions across the mammalian genome, associated with both protein-coding and rRNA genes. Within the rDNA, the distribution of ß-actin correlated with NM1 and the other subunits of the B-WICH complex, WSTF and SNF2h. In ß-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 ß-actin, in contrast to mutated forms with polymerization defects, efficiently rescued rRNA synthesis underscoring the direct role for a polymerization-competent form of ß-actin in Pol I transcription. The rRNA synthesis defects in the ß-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 ß-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 ß-actin knockouts, epigenetic reprogramming and rDNA transcription inactivation lead to growth and proliferation defects.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ADN Ribosómico
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Actinas
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Regulación del Desarrollo de la Expresión Génica
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Epigénesis Genética
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Reprogramación Celular
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Fibroblastos
Límite:
Animals
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2016
Tipo del documento:
Article