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Glycogen synthase kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

ABSTRACT: Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation.

ORGANISM(S): Mus musculus

PROVIDER: GSE57153 | GEO | 2014/05/02

SECONDARY ACCESSION(S): PRJNA245795

REPOSITORIES: GEO

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Glycogen synthase kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Project description:Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation. Examination of GSK3beta with the genome in mouse embryonic fibroblasts

2014-05-02 | E-GEOD-57153 | biostudies-arrayexpress

Nuclear myosin 1 contributes to a chromatin landscape compatible with RNA polymerase II transcription activation

Project description:Nuclear myosin 1c (NM1) is emerging as regulator of transcription and chromatin organization. Using a genome-wide approach we report here that NM1 binds across the mammalian genome with occupancy peaks at class II gene promoters, correlating with distributions of RNA Polymerase II (Pol II) and active epigenetic marks. We show that NM1 synergizes with polymerase-associated actin to maintain active Pol II at gene promoters. NM1 also co-localizes with the nucleosome remodeler SNF2h at class II promoters where they assemble together with WSTF as part of the B-WICH complex to remodel chromatin. Following B-WICH assembly, NM1 mediates physical recruitment of the histone acetyl transferase PCAF and the histone methyl transferase Set1/Ash2 to maintain and preserve H3K9acetylation and H3K4trimethylation for active transcription. We propose a novel genome-wide mechanism where myosin synergizes with Pol II-associated actin to link the polymerase machinery with permissive chromatin for transcription activation. Association of nuclear myosin 1 (NM1) with the genome in mouse embryonic fibroblasts

2015-05-04 | E-GEOD-66542 | biostudies-arrayexpress

Nuclear myosin 1 contributes to a chromatin landscape compatible with RNA polymerase II transcription activation

2015-05-04 | GSE66542 | GEO

Diurnal changes of HDAC3, Rev-erbα, NCoR and Pol II recruitment to the mouse liver genome and of H3K9Ac

Project description:We reported a diurnal changes in the recruitment of HDAC3, Rev-erbα, NCoR and Pol II to the mouse liver genome as well as H3K9 acetylation in vivo at ZT10 and ZT22. ChIP-Seq profiling of HDAC3, Rev-erbα, NCoR and Pol II binding and H3K9Ac in mouse liver harvested at 2 different times (ZT10 and ZT22) of the day

2011-03-11 | E-GEOD-26345 | biostudies-arrayexpress

Genome-wide analysis distinguishes hyperglycemia regulated epigenetic signatures of primary vascular cells (gene expression)

Project description:We report that hyperglycemia-mediated induction of genes and pathways associated to endothelial dysfunction occur through modulation of acetylated H3K9/K14 inversely correlated with methyl-CpG content. Examination of H3K9/K14 histone acetylation and DNA methylation in hyperglycemic conditions. see GSE29251 for histone acetylation and DNA methylation

2011-07-19 | E-GEOD-30780 | biostudies-arrayexpress

Diurnal changes of HDAC3, Rev-erbα, NCoR and Pol II recruitment to the mouse liver genome and of H3K9Ac

Project description:We reported a diurnal changes in the recruitment of HDAC3, Rev-erbα, NCoR and Pol II to the mouse liver genome as well as H3K9 acetylation in vivo at ZT10 and ZT22.

2011-03-11 | GSE26345 | GEO

Nuclear Myosin I regulates genome stability by controlling p21 gene activation through a chromatin-based mechanism

Project description:Nuclear myosin 1 (NM1) has been implicated in key nuclear functions. Here, we show NM1 has a global role in chromatin regulation and this likely impacts global transcription. High-content phenotypic profiling and transcriptional profiling by RNA-Seq on NM1 KO mouse embryonic fibroblasts show extensive chromatin alteration and differential gene expression compared to a WT condition. In particular, NM1 deletion leads to significant upregulation of genes involved in DNA damage response and cell cycle, which is further supported by increased DNA damage revealed by increased γ-H2AX foci number and proliferation rate. We found that upon DNA damage, NM1 directly regulates expression of Cdkn1A (p21) and binds to p53. NM1 recruits histone acetyl-transferase PCAF and histone methyl-transferase Set1 to p21 promoter for histone H3 acetylation and methylation, facilitating Cdkn1A gene transcription. We propose that NM1 regulates the transcriptional response upon DNA damage and imply an involvement for NM1 in genome stability.

2019-06-29 | GSE133506 | GEO

Genome-wide analysis distinguishes hyperglycemia regulated epigenetic signatures of primary vascular cells (ChIP-seq)

2011-06-01 | E-GEOD-29251 | biostudies-arrayexpress

In beta-actin knockout mouse embryonic fibroblasts epigenetic reprogramming and chromatin modifications lead to rDNA transcription inactivation and defects in cell growth and proliferation

Project description:Actin and nuclear myosin 1 (NM1) are emerging as regulators of transcription and chromatin organization. Using a genome-wide approach we report here that β-actin binds both intergenic and genic regions across the entire mammalian genome, associated with both protein-coding and rRNA genes. Across the rDNA transcription unit 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 are down-regulated concomitantly with drops in Pol I and NM1 occupancies across the rRNA gene. In knock-in experiments, reintroduction of wild-type β-actin but not mutated forms with polymerization defects, rescued rRNA synthesis underscoring the direct role for β-actin in Pol I transcription and the importance of polymerization during the transcription process. The rRNA defects in the β-actin-/-MEFs are accompanied by epigenetic reprogramming that leads to up-regulation of the repressive mark H3K4me1. In addition, a high resolution chromatin accessibility assay showed that the absence of β-actin leads to a more compact chromatin at specific locations, including promoter-proximal enhancer (T0 sequence) and Sal boxes (T1-T10), disturbing binding of the transcription termination factor 1 (TTF1). We propose a novel mechanism where the polymerase-associated β-actin synergizes with NM1 to coordinate the establishment of permissive chromatin with the correct rDNA topology for Pol I transcription enhancement.

2015-10-04 | GSE68686 | GEO

ChIP-seq analysis of H3K9 acetylation enrichment in hESCs and day 8 neural progenitor cells

Project description:H3K9 acetylation was enriched in pluripotency genes in hESCs and in neural genes in neural progenitor cells Examination of H3K9 acetylation distributions in hESCs and neural progenitor cells

2015-03-11 | E-GEOD-66778 | biostudies-arrayexpress

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