Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

H3K9 methylation-independent activity for HPL-2/HP1 in heterochromatin foci, gene repression, and organogenesis

ABSTRACT: Differentiated cells rely on segregation of the genome into heterochromatin and euchromatin, but the mechanisms that establish these domains in vivo are incompletely understood. The current models suggest that heterochromatin is marked by histone H3 lysine 9 methylation (H3K9me), which recruits heterochromatin protein 1 (HP1), to compact chromatin and repress transcription. In C. elegans, the SETDB1 homolog MET-2 is essential for H3K9me-mediated gene silencing; however, MET-2 also localizes to heterochromatic foci independently of H3K9me and exhibits non-catalytic functions that support both germline and somatic development. Here we extend these findings by examining the classical H3K9me reader HP1. We show that HPL-2/HP1 deficient in methyl-lysine binding or in the absence of H3K9me can still repress transcription, promote organogenesis and localize to heterochromatin foci. Whereas activity remains in the absence of the HPL-2:H3K9me interaction, complete loss of met-2 and hpl-2 shows synergistic phenotypes for organogenesis and gene de-repression, underscoring the existence of additional, H3K9me-independent functions. HPL-2 and MET-2 require distinct binding partners for their localization and activity: MET-2 associates with the disordered protein LIN-65/ATF7IP, while HPL-2 depends on the multi-zinc finger protein LIN-13, which interacts with the HPL-2 chromoshadow domain. Our findings suggest that HPL-2 and MET-2 operate in parallel pathways, localizing to heterochromatic foci and promoting gene silencing and organogenesis, with H3K9me acting as a reinforcing, but non-essential, element in these processes.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE278459 | GEO | 2025/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

An unstructured MET-2/SETDB1 cofactor ensures H3K9me2, focus formation and perinuclear anchoring [RNA-seq]

Project description:The segregation of the genome into accessible euchromatin and histone H3 lysine 9 methylated (H3K9me) heterochromatin is essential for the repression of repetitive elements and tissue-specific genes. In C. elegans, the SETDB1 homolog MET-2 catalyzes H3K9me1 and me2. In worms as in vertebrates, the regulation of this crucial enzyme remains enigmatic. Contrary to the localization of overexpressed MET-2, we find endogenous MET-2 to be nuclear throughout development, enriched in perinuclear foci in a cell cycle-dependent manner. We show by mass spectrometry that MET-2 associates with a highly unstructured protein, LIN-65, and a conserved GTPase effector ARLE-14. All three colocalize at heterochromatic foci. Ablation of lin-65, but not arle-14, mislocalizes and destabilizes MET-2, resulting in decreased H3K9me2, derepression of MET-2 targets, and loss of fertility. Importantly, mutation of met-2 or lin-65 is sufficient to disrupt the perinuclear clustering of heterochromatin genome-wide. Thus, LIN-65 is an essential cofactor of MET-2 required for H3K9me2 deposition, heterochromatin clustering, perinuclear anchoring, and transcriptional repression.

2019-02-06 | GSE122339 | GEO

An unstructured MET-2/SETDB1 cofactor ensures H3K9me2, focus formation and perinuclear anchoring [ChIP-seq]

2019-02-06 | GSE122335 | GEO

A structural role for histone methyltransferase MET-2 represses transcription independent of H3K9me catalysis [RNA-seq]

Project description:Packaging genomic regions into silenced heterochromatin is critical to maintain organismal viability and tissue identity. Methylation of histone H3 on lysine 9 (H3K9me) marks heterochromatin. Here we show that in addition to catalyzing H3K9me, the C. elegans histone methyltransferase MET-2 (SETDB1-like) has a second non-catalytic function that can itself contribute to gene repression. We find that subnuclear concentrates, or foci, of MET-2 correlate with efficient HMT activity, yet foci composed of catalytic-deficient MET-2 are also able to mediate transcriptional silencing. Genetic ablation of met-2 or physiological disruption of MET-2 foci by heat stress results in loss of silencing coincident with an increase in histone acetylation. Restoration of catalytically deficient MET-2 foci mitigates H3K9 and H3K27 hyperacetylation, gene derepression, and infertility, demonstrating a structural role for foci of a conserved heterochromatic histone methyltransferase in gene silencing independent of its enzymatic activity.

2021-08-01 | GSE168924 | GEO

A structural role for histone methyltransferase MET-2 represses transcription independent of H3K9me catalysis [ChIP-seq]

2021-08-01 | GSE168923 | GEO

H3K9 methylation-independent activity for HPL-2/HP1 in heterochromatin foci, gene repression, and organogenesis

Project description:H3K9 methylation-independent activity for HPL-2/HP1 in heterochromatin foci, gene repression, and organogenesis

| PRJNA1167308 | ENA

Relics of repeat-induced point mutation direct heterochromatin formation in Neurospora crassa

Project description:Both RNAi-dependent and -independent mechanisms have been implicated in the establishment of heterochromatin domains, which may be stabilized by feedback loops involving chromatin proteins and modifications of histones and DNA. Neurospora crassa sports features of heterochromatin found in higher eukaryotes, namely cytosine methylation (5mC), methylation of histone H3 lysine9 (H3K9me) and HETEROCHROMATIN PROTEIN-1 (HP1), and provides a model to investigate heterochromatin establishment and maintenance. We mapped the distribution of HP1, 5mC, H3K9me3 and H3K4me2 at 100bp-resolution and explored their interplay. HP1, H3K9me3 and DNA methylation were extensively colocalized and defined 44 heterochromatic domains on linkage group VII, all relics of repeat-induced point mutation (RIP). Interestingly, the centromere was found in a striking ~350kb heterochromatic domain with no detectable H3K4me2. 5mC was not found in genes, in contrast to the situation in plants and animals. H3K9me3 is required for HP1 localization and DNA methylation. Here, we show that localization of H3K9me3 is independent of 5mC or HP1 at virtually all heterochromatin regions. In addition, we observed complete restoration of DNA methylation patterns after depletion and reintroduction of the H3K9 methylation machinery, indicating that the signals for de novo heterochromatin formation lie upstream of H3K9 methylation. These data show that A:T rich RIPâd DNA efficently directs methylation of H3K9, which in turn, directs methylation of associated cytosines. Immunoprecipitation experiments using antibodies to 5mC, H3K9me3, epitope-tagged HP1, and H3K4me2 were performed. The immunoprecipitate fraction was labeled with Cy5 and the total input was labeled with Cy3. Samples were hybridized to a N. crassa LGVII tiling path microarray.

2010-05-15 | E-GEOD-12690 | biostudies-arrayexpress

A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress [RNA-seq]

Project description:Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among these factors and pathways underlies the importance of safeguarding the genome through multiple means.

2017-03-11 | GSE87523 | GEO

A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress [ChIP-seq]

2017-03-11 | GSE87522 | GEO

An RNA Endonuclease-Kinase Complex Required for Spreading and Epigenetic Inheritance of Heterochromatin

Project description:The highly conserved multienzyme Rix1-containing complex (hereafter referred to as the rixosome), is required for ribosomal RNA (rRNA) processing and also localizes to heterochromatin in fission yeast, but its role in heterochromatin formation is unknown. Here we report the isolation of separation of function mutations in subunits of the rixosome that abolish its physical association with Swi6/HP1 and localization to heterochromatin, but do not affect growth or rRNA processing. These mutations abolish the epigenetic inheritance of silencing and histone H3 lysine 9 methylation (H3K9me), accumulate heterochromatic RNAs, and cannot spread H3K9me and silencing away from nucleation sites into an inserted transgene. We further show that the rixosome acts upstream of the conserved 5’-3’ exoribonuclease Dhp1/XRN2 to promote heterochromatic RNA degradation. These findings reveal a new RNA degradation pathway that specifically localizes to heterochromatin to degrade nascent transcripts and enable heterochromatin spreading and inheritance.

2020-06-08 | GSE140920 | GEO

Aberrant heterochromatic foci are associated to deregulation of the GMCL1 gene in CH1 lymphoma B cells

Project description:Chromosome 1 pericentric heterochromatin rearrangements : potent drivers of nuclear architecture perturbations and gene deregulation in human B cell lymphoma Epigenetic perturbations are increasingly described in cancer cells where they are thought to contribute to deregulated gene expression and genome instability. Here, we report the first evidence, that a distinct category of chromosomal translocation observed in human tumours â those targeting 1q12 satellite DNA - can directly mediate such perturbations by promoting the formation of aberrant heterochromatic foci (aHCF). By detailed investigations of a 1q12 translocation to chromosome 2p, in a case of human B cell lymphoma, aberrant aHCF were shown to be localised to the nuclear periphery and to arise as a consequence of long range âpairingâ between the translocated 1q12 and chromosome 2 centromeric regions. Remarkably, adjacent 2p sequences showed increased levels of repressive histone modifications, including H4K20me3 and H3K9me3, and were bound by HP1. aHCF were associated to aberrant spatial localisation and deregulated expression of a novel 2p gene (GMCL1) that was found to have prognostic impact in B cell lymphoma. Thus constitutive heterochromatin rearrangements can contribute to tumourigenesis by perturbing gene expression by via long range epigenetic mechanisms. The formation of aberrant heterochromatic foci, coupled to abnormal enrichment of adjacent 2p sequences in repressive heterochromatin marks (H4K20me3, H3K9me3 and HP1), delayed replication and repositioning of the rearranged chromosome 2 to the nuclear periphery, could be associated to altered gene expression of at least those genes brought into close proximity to heterochromatin. To assess this question, global gene expression profiling was performed in the lymphoma B cells presenting the aberrant heterochromatin foci (CH1), treated or not with the histone deacetylase inhibitor, trichostatin A.

2010-03-23 | E-GEOD-20666 | biostudies-arrayexpress

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