Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Clr4SUV39H1 ubiquitination and non-coding RNA mediate transcriptional silencing via heterochromatic phase transitions

ABSTRACT: Transcriptional silencing by RNAi paradoxically relies on transcription, but how the transition from transcription to silencing is achieved has remained unclear. The Cryptic Loci Regulator complex (CLRC) in Schizosaccharomyces pombe is a cullin-ring E3 ligase required for silencing that is recruited by RNAi. We found that the E2 ubiquitin conjugating enzyme Ubc4 interacts with CLRC and mono-ubiquitinates the histone H3K9 methyltransferase Clr4SUV39H1, promoting the transition from co-transcriptional gene silencing (H3K9me2) to transcriptional gene silencing (H3K9me3). Ubiquitination of Clr4 occurs in an intrinsically disordered region (IDR), which undergoes robust liquid-liquid phase separation (LLPS), along with Swi6HP1 the effector of transcriptional gene silencing. Phase separation of Clr4 and Swi6 is exquisitely sensitive to non-coding RNA (ncRNA), which promotes dimerization, chromatin association, and di-, but not tri- methylation instead. Ubc4-CLRC also targets the transcriptional co-activator Bdf2BRD4, down-regulating centromeric transcription and small RNA production. The deubiquitinase Ubp3 counteracts both activities.

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE156069 | GEO | 2024/02/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Histone H2A.Z cooperates with RNAi and heterochromatin factors to suppress antisense RNAs

2009-08-25 | GSE17271 | GEO

Histone H2A.Z cooperates with RNAi and heterochromatin factors to suppress antisense RNAs

Project description:Expression profile of mutant cells compared to wild-type cells: Expression profile of Schizosaccharomyces pombe genome in ∆pht1, ∆ago1, ∆clr4, rik1, ∆pht1rik1, ∆pht1∆ago1 and ∆pht1∆clr4 cells. Expression profile of Schizosaccharomyces pombe genome in ∆rrp6, ∆cid14, ∆swi6, ∆swr1, ∆set1, ∆pht1∆swi6 and ∆pht1∆set1 cells. Expression profile of Schizosaccharomyces pombe genome in ∆alp13, ∆cph1, ∆set2, clr6-1 and ∆cph1∆pht1 cells. Occupancy profiling: Occupancy profiling of RNA polymerase II, histone variant H2A.Z and ClrC subunit Rik1 in fission yeast Schizosaccharomyces pombe Occupancy profiling of histone variant H2A.Z in ∆msc1 cells. Agilent 60mer oligonucleotide custom array containing probes spanning large portion of chromosome 2 at 50bp resolution was used to profile expression levels in mutant cells and to compare them to levels in wild-type cells. Agilent 60mer array was used to analyze DNA recovered by immunoprecipitation of RNA polymerase II, H2A.Z or Rik1 from asynchronous culture of fission yeast. Agilent 60mer array was used to analyze DNA recovered by immunoprecipitation of histone H2A.Z from asynchronous culture of fission yeast.

2009-08-25 | E-GEOD-17271 | biostudies-arrayexpress

Phosphorylation of HP1/Swi6 relieves competition with Suv39/Clr4 on nucleosomes and enables H3K9 trimethyl spreading.

Project description:Heterochromatin formation in Schizosaccharomyces pombe requires the spreading of histone 3 (H3) Lysine 9 (K9) methylation (me) from nucleation centers by the H3K9 methylase, Suv39/Clr4, and the reader protein, HP1/Swi6. To accomplish this, Suv39/Clr4 and HP1/Swi6 have to associate with nucleosomes both nonspecifically, binding DNA and octamer surfaces and specifically, via recognition of methylated H3K9 by their respective chromodomains. However, how both proteins avoid competition for the same nucleosomes in this process is unclear. Here, we show that phosphorylation tunes the nucleosome affinity of HP1/Swi6 such that it preferentially partitions onto Suv39/Clr4’s trimethyl product rather than its unmethylated substrates. Preferential partitioning enables efficient conversion from di-to trimethylation on nucleosomes in vitro and H3K9me3 spreading in vivo. Together, our data suggests that phosphorylation of HP1/Swi6 creates a regime that relieves competition with the “read-write” mechanism of Suv39/Clr4 for productive heterochromatin spreading.

2024-12-02 | GSE271394 | GEO

Abo1 is required for H3K9me2 to H3K9me3 transition in telomeric and centromeric heterochromatin [ChIP-seq]

Project description:Regulation of heterochromatin is critical for genome stability. Different states of methylated H3K9 have been discovered with distinct roles in heterochromatin formation and silencing. However, the control of the transition from H3K9me2 to H3K9me3 is still unclear. Here we investigate the role of the conserved bromodomain AAA-ATPase, Abo1, involved in maintaining the global nucleosome organization in fission yeast. We identified several key factors involved in heterochromatin silencing to interact genetically with Abo1: the histone deacetylase Clr3, the H3K9 methyltransferase Clr4, and the HP1 homologue Swi6. Cells lacking Abo1 display an imbalance of H3K9me2 and H3K9me3 in heterochromatin. In abo1∆ cells, the centromeric constitutive heterochromatin had increased H3K9me2 but decreased H3K9me3 levels compared to wild type. In contrast, facultative heterochromatin regions, show both reduced H3K9me2 and H3K9me3 levels in abo1∆. Genome-wide analysis showed that abo1∆ cells have silencing defects in both centromeres and subtelomeres, but not in a subset of heterochromatin islands. Our work uncovers a new role for Abo1 in supporting Clr4 activity and allowing for the transition of H3K9me2 to H3K9me3 in telomeric and centromeric heterochromatin.

2020-04-13 | GSE125911 | GEO

Role of CLRC complex in telomeric assembly of shelterin proteins

Project description:Heterochromatin represents a specific structural organization of chromatin that is essential for cellular development and genome stability. In S. pombe, all members of the Cul4-Rik1Raf1/2 E3 ubiquitin ligase complex are critical for heterochromatin integrity. This key complex assembles with Clr4 (the sole H3K9 methyltransferase) to form the CLRC, which is required for silencing of the three main heterochromatic regions (centromere, telomeres and mating locus). Although much effort has been invested in understanding the function of this key complex, the ubiquitylation substrate(s) of CLRC remain unknown. To overcome the challenge of transient interactions between substrate and ubiquitin ligase in vivo, we have established the Ubiquitin Ligase Trapping method in S. pombe (Mark KG et al., Mol. Cell 2014). This approach is based on fusing a ubiquitin associated domain (UBA) to the E3 ligase by a flexible linker in order to trap the ubiquitylated substrate allowing the analysis of E3-associated proteins by mass spectrometry. We have been able to reproducibly detect chromatin related proteins associated with CRLC and to validate their interactions. Interestingly, among these candidates we identified the telomeric shelterin complex as a new interactor of CLRC.

2019-02-19 | PXD003834 | Pride

The establishment of HP1-independent heterochromatin reveals an essential role for HP1 proteins in maintaining epigenetic memory.

Project description:H3K9 methylation (H3K9me) marks transcriptionally silent genomic regions called heterochromatin. A conserved class of HP1 proteins are critically required to establish and maintain heterochromatin. HP1 proteins bind to H3K9me, recruit factors that promote heterochromatin formation, and oligomerize to form phase-separated condensates. We do not understand how HP1 protein binding to heterochromatin establishes and maintains transcriptional silencing. Here, we demonstrate that the S.pombe HP1 homolog, Swi6, can be completely bypassed to establish silencing at ectopic and endogenous loci when an H3K4 methyltransferase, Set1 and an H3K14 acetyltransferase, Mst2 are deleted. Deleting Set1 and Mst2 enhances Clr4 enzymatic activity, leading to higher H3K9me levels and increased spreading. In contrast, Swi6 and its capacity to oligomerize were indispensable during epigenetic maintenance. Our results demonstrate the role of HP1 proteins in regulating histone modification crosstalk during establishment and identifies a genetically separable function in maintaining epigenetic memory.

2023-05-24 | GSE233333 | GEO

The establishment of HP1-independent heterochromatin reveals an essential role for HP1 proteins in maintaining epigenetic memory

2023-05-10 | GSE231618 | GEO

Uncoupling the distinct functions of HP1 proteins during heterochromatin establishment and maintenance

2023-09-26 | GSE244017 | GEO

Abo1 is required for H3K9me2 to H3K9me3 transition in telomeric and centromeric heterochromatin [gene expression]

2020-04-13 | GSE125910 | GEO

DamID for Swi6, Rdp1 and Dcr1 in Schizosaccharomyces pombe

Project description:In the fission yeast Schizosaccharomyces pombe, the RNA interference (RNAi) pathway is required to generate small interfering RNAs (siRNAs) that mediate heterochromatic silencing of centromeric repeats. Here we demonstrate that RNAi also functions to repress genomic elements other than constitutive heterochromatin. Using DamID (DNA adenine methyltransferase identification) we show that Dcr1 and Rdp1 physically associate with some euchromatic genes, non-coding RNA (ncRNA) genes, and retrotransposon long terminal repeats (LTRs), and that this association is independent of the Clr4 histone methyltransferase. Physical association of RNAi with chromatin is sufficient to trigger a silencing response but not to assemble heterochromatin. The mode of silencing at the newly identified RNAi targets is consistent with a co-transcriptional gene silencing model as proposed earlier and functions with trace amounts of siRNAs. We anticipate that similar mechanisms could also be operational in other eukaryotes.

2010-09-25 | GSE24360 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data