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TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE142488 | GEO | 2020/12/22

REPOSITORIES: GEO

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TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation.

Project description:Cell proliferation and differentiation require signalling pathways that enforce appropriate and timely gene expression. We find that Tor2, the catalytic subunit of the TORC1 complex in fission yeast, targets a conserved nuclear RNA elimination network, particularly the serine and proline-rich protein Pir1, to control gene expression through RNA decay and facultative heterochromatin assembly. Phosphorylation by Tor2 protects Pir1 from degradation by the ubiquitin-proteasome system involving the polyubiquitin Ubi4 stress-response protein and the Cul4-Ddb1 E3 ligase. This pathway suppresses widespread and untimely gene expression and is critical for sustaining cell proliferation. Moreover, we find that the dynamic nature of Tor2-mediated control of RNA elimination machinery defines gene expression patterns that coordinate fundamental chromosomal events during gametogenesis, such as meiotic double-strand-break formation and chromosome segregation. These findings have important implications for understanding how the TOR signalling pathway reprogrammes gene expression patterns and contributes to diseases such as cancer.

| S-EPMC9260697 | biostudies-literature

TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation

Project description:TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation

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TOR targets a nuclear RNA processing network to support cell proliferation and control developmental gene expression [ChIP-chip]

Project description:Occupancy profiling of lysine 9 dimethylated histone H3 in fission yeast. Occupancy profiling of MYC-tagged or GFP-tagged Pir1 protein in fission yeast. Occupancy profiling of FLAG-tagged Rec12-DNA linkages during meiosis of fission yeast.

2020-12-22 | GSE142486 | GEO

TOR targets RNA elimination machinery to govern facultative heterochromatin assembly and mitosis to meiosis developmental switch [RNA-seq]

Project description:RNA sequencing in Schizosaccharomyces pombe

2020-12-22 | GSE142487 | GEO

Histone deacetylation promotes transcriptional silencing at facultative heterochromatin.

Project description:It is important to accurately regulate the expression of genes involved in development and environmental response. In the fission yeast Schizosaccharomyces pombe, meiotic genes are tightly repressed during vegetative growth. Despite being embedded in heterochromatin these genes are transcribed and believed to be repressed primarily at the level of RNA. However, the mechanism of facultative heterochromatin formation and the interplay with transcription regulation is not understood. We show genome-wide that HDAC-dependent histone deacetylation is a major determinant in transcriptional silencing of facultative heterochromatin domains. Indeed, mutation of class I/II HDACs leads to increased transcription of meiotic genes and accumulation of their mRNAs. Mechanistic dissection of the pho1 gene where, in response to phosphate, transient facultative heterochromatin is established by overlapping lncRNA transcription shows that the Clr3 HDAC contributes to silencing independently of SHREC, but in an lncRNA-dependent manner. We propose that HDACs promote facultative heterochromatin by establishing alternative transcriptional silencing.

| S-EPMC6009587 | biostudies-literature

TOR targets a nuclear RNA processing network to support cell proliferation and control developmental gene expression [ChIP-chip]

Project description:TOR targets a nuclear RNA processing network to support cell proliferation and control developmental gene expression [ChIP-chip]

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Enhancer of Rudimentary Cooperates with Conserved RNA-Processing Factors to Promote Meiotic mRNA Decay and Facultative Heterochromatin Assembly.

Project description:Erh1, the fission yeast homolog of Enhancer of rudimentary, is implicated in meiotic mRNA elimination during vegetative growth, but its function is poorly understood. We show that Erh1 and the RNA-binding protein Mmi1 form a stoichiometric complex, called the Erh1-Mmi1 complex (EMC), to promote meiotic mRNA decay and facultative heterochromatin assembly. To perform these functions, EMC associates with two distinct complexes, Mtl1-Red1 core (MTREC) and CCR4-NOT. Whereas MTREC facilitates assembly of heterochromatin islands coating meiotic genes silenced by the nuclear exosome, CCR4-NOT promotes RNAi-dependent heterochromatin domain (HOOD) formation at EMC-target loci. CCR4-NOT also assembles HOODs at retrotransposons and regulated genes containing cryptic introns. We find that CCR4-NOT facilitates HOOD assembly through its association with the conserved Pir2/ARS2 protein, and also maintains rDNA integrity and silencing by promoting heterochromatin formation. Our results reveal connections among Erh1, CCR4-NOT, Pir2/ARS2, and RNAi, which target heterochromatin to regulate gene expression and protect genome integrity.

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Taz1-Shelterin promotes facultative heterochromatin assembly at chromosome-internal sites containing late replication origins

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-06-09 | E-GEOD-78823 | biostudies-arrayexpress

RNA elimination machinery targeting meiotic mRNAs promotes facultative heterochromatin formation.

Project description:Facultative heterochromatin that changes during cellular differentiation coordinates regulated gene expression, but its assembly is poorly understood. Here, we describe facultative heterochromatin islands in fission yeast and show that their formation at meiotic genes requires factors that eliminate meiotic messenger RNAs (mRNAs) during vegetative growth. Blocking production of meiotic mRNA or loss of RNA elimination factors, including Mmi1 and Red1 proteins, abolishes heterochromatin islands. RNA elimination machinery is enriched at meiotic loci and interacts with Clr4/SUV39h, a methyltransferase involved in heterochromatin assembly. Heterochromatin islands disassemble in response to nutritional signals that induce sexual differentiation. This process involves the antisilencing factor Epe1, the loss of which causes dramatic increase in heterochromatic loci. Our analyses uncover unexpected regulatory roles for mRNA-processing factors that assemble dynamic heterochromatin to modulate gene expression.

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Iron homeostasis regulates facultative heterochromatin assembly in adaptive genome control.

Project description:Iron metabolism is critical for sustaining life and maintaining human health. Here, we find that iron homeostasis is linked to facultative heterochromatin assembly and regulation of gene expression during adaptive genome control. We show that the fission yeast Clr4/Suv39h histone methyltransferase is part of a rheostat-like mechanism in which transcriptional upregulation of mRNAs in response to environmental change provides feedback to prevent their uncontrolled expression through heterochromatin assembly. Interestingly, proper iron homeostasis is required, as iron depletion or downregulation of iron transporters causes defects in heterochromatin assembly and unrestrained upregulation of gene expression. Remarkably, an unbiased genetic screen revealed that restoration of iron homeostasis is sufficient to re-establish facultative heterochromatin and proper gene control genome-wide. These results establish a role for iron homeostasis in facultative heterochromatin assembly and reveal a dynamic mechanism for reprogramming the genome in response to environmental changes.

| S-EPMC5936480 | biostudies-literature

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