Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PHF2 maintains neural progenitor genome stability by preserving pericentric heterochromatin integrity (ChIP-Seq)

ABSTRACT: Heterochromatin stability is crucial for progenitor proliferation during development. It relays on the maintenance of local hubs of H3K9me. However, the mechanisms underlying the establishment of competent local levels of H3K9me remain poorly understood. To address this intriguing question, we used a neural stem cell (NSC) model to analyze the significance of the H3K9me2 demethylase PHF2, which is crucial for progenitor proliferation. Through mass spectroscopy and genome-wide assays, we uncovered that PHF2 interacts with heterochromatin components and it is enriched at pericentromeric heterochromatin (PcH) boundaries. This binding is essential for maintaining silenced the satellite repeats and to prevent DNA damage and genome instability. To do that, PHF2 balances H3K9me3 levels at these boundaries to ensure high H3K9me3 levels at satellite repeats. Mechanistically, we discover that while its catalytic and PHD domains are indispensable, the intrinsically disordered region within PHF2 is dispensable for stabilizing PcH. Altogether, our study sheds light on the intricate relationship between heterochromatin stability and progenitor proliferation during mammalian neurogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE242383 | GEO | 2024/06/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

PHF2-mediated H3K9me balance orchestrates heterochromatin stability and progenitor proliferation in early neurogenesisPHF2-mediated H3K9me balance orchestrates heterochromatin stability and progenitor proliferation in early neurogenesis

Project description:Heterochromatin stability is crucial for progenitor proliferation during early neurogenesis. It relays on the maintenance of local hubs of H3K9me. However, the current understanding of the processes involved in the formation of efficient localized levels of H3K9me remains limited. To address this intriguing question, we used a neural stem cell (NSC) to analyze the function of the H3K9me2 demethylase PHF2, which is crucial for progenitor proliferation. Through mass spectroscopy and genome-wide assays, we uncovered that PHF2 interacts with heterochromatin components and it is enriched at pericentromeric heterochromatin (PcH) boundaries. This binding is essential for maintaining silenced the satellite repeats thereby preventing DNA damage and genome instability. Depletion of PHF2 led to increased transcription of heterochromatic repeats, accompanied by a decrease in H3K9me3 levels and alterations in PcH organization. Further analysis revealed that PHF2's PHD and catalytic domains are crucial for maintaining PcH stability and preventing unscheduled repeat transcription, thereby safeguarding genome integrity. These results highlight the multifaceted nature of PHF2's functions in maintaining heterochromatin stability and regulating gene expression during neural development. Altogether, our study unravels the intricate relationship between heterochromatin stability and progenitor proliferation during mammalian neurogenesis, shedding light on its potential as a therapeutic target for neurodevelopmental disorders

2024-06-11 | PXD051336 | Pride

PHF2 maintains neural progenitor genome stability by preserving pericentric heterochromatin integrity (ATAC-Seq)

Project description:Heterochromatin stability is crucial for progenitor proliferation during development. It relays on the maintenance of local hubs of H3K9me. However, the mechanisms underlying the establishment of competent local levels of H3K9me remain poorly understood. To address this intriguing question, we used a neural stem cell (NSC) model to analyze the significance of the H3K9me2 demethylase PHF2, which is crucial for progenitor proliferation. Through mass spectroscopy and genome-wide assays, we uncovered that PHF2 interacts with heterochromatin components and it is enriched at pericentromeric heterochromatin (PcH) boundaries. This binding is essential for maintaining silenced the satellite repeats and to prevent DNA damage and genome instability. To do that, PHF2 balances H3K9me3 levels at these boundaries to ensure high H3K9me3 levels at satellite repeats. Mechanistically, we discover that while its catalytic and PHD domains are indispensable, the intrinsically disordered region within PHF2 is dispensable for stabilizing PcH. Altogether, our study sheds light on the intricate relationship between heterochromatin stability and progenitor proliferation during mammalian neurogenesis.

2024-09-12 | GSE242384 | GEO

Specificity, propagation and memory of pericentric heterochromatin in mouse fibroblasts

Project description:We assembled a quantitative map for the abundance and interactions of 16 factors related to PCH in living cells and found that stably bound complexes of the histone methyltransferase Suv39h1/2 demarcate the PCH state. From the experimental data we developed a predictive mathematical model that explains how chromatin-bound Suv39h1/2 complexes act as nucleation sites and propagate a spatially confined PCH domain with elevated histone H3 trimethylation levels via chromatin dynamics. Enrichment of HP1, Suv39h1/h2, H3K9me3 and H3K36me3 was assessed by ChIP-seq in NPCs derived from ESCs showing differential occupation at intergenic major satellite repeats and enrichment of heterochromatin factors. ChIP-seq of HP1, Suv39h1, Suv39h2, H3K9me3, H3K36me3 in NPCs

2014-08-12 | E-GEOD-58555 | biostudies-arrayexpress

Specificity, propagation and memory of pericentric heterochromatin in mouse fibroblasts

2014-08-12 | GSE58555 | GEO

ChIP-seq experiment of PHF2 and H3K9me2 in NSCs

Project description:Histone H3 lysine 9 methylation (H3K9me) is essential for cellular homeostasis; however, its contribution to development is not well established. Here, we demonstrate that the H3K9me2 demethylase PHF2 is essential for neural progenitor proliferation in vitro and for early neurogenesis in the chicken spinal cord. Using genome-wide analyses and biochemical assays we show that PHF2 controls the expression of critical cell cycle progression genes, particularly those related to DNA replication, by keeping low levels of H3K9me3 at promoters. Accordingly, PHF2 depletion induces R-loop accumulation that leads to extensive DNA damage and cell cycle arrest. These data reveal a role of PHF2 as a guarantor of genome stability that allows proper expansion of neural progenitors during development.

2019-09-10 | GSE122263 | GEO

RNA-seq experiment of shControl and shPHF2 NSCs

2019-09-10 | GSE122264 | GEO

A transcription factor based mechanism for mouse heterochromatin formation

Project description:We identify Pax3 and Pax9 transcription factors (TFs) as important regulators of mouse heterochromatin. Simultaneous depletion of these factors results in loss of H3K9me3 from Major Satellite repeats and dramatic transcript overexpression. H3K9me3 enrichment at intergenic major satellite repeats is only present if these sequences retain intact Pax and other TF binding sites. H3K9me3 ChIP-seq in mouse ES cells wt and Pax3 KO and Pax3 KO/Pax9 KD

2012-09-16 | E-GEOD-40086 | biostudies-arrayexpress

DOT1L regulates pericentromeric heterochromatin

Project description:Many repetitive DNA elements are packaged in heterochromatin, but depend on occasional transcription to maintain long-term silencing. The factors that promote transcription of repeat elements in heterochromatin are largely unknown. Here, we show that DOT1L, a histone methyltransferase that modifies lysine 79 of histone H3 (H3K79), is required for transcription of major satellite repeats to maintain pericentromeric heterochromatin (PCH), and that this function is essential for preimplantation development. DOT1L is a transcriptional activator at single-copy genes but does not have a known role in repeat element transcription. We show that H3K79me3 is specifically enriched at repetitive elements, that loss of DOT1L compromises pericentromeric major satellite transcription, and that this function depends on interaction between DOT1L and the chromatin remodeler SMARCA5. DOT1L inhibition causes chromosome breaks and cell cycle defects, and leads to embryonic lethality. Together, our findings uncover a vital new role for DOT1L in transcriptional activation of heterochromatic repeats.

2023-05-26 | PXD028824 | Pride

LSD1 Prevents Aberrant Heterochromatin Formation in Neurospora crassa

Project description:Heterochromatin is a specialized form of chromatin that restricts access to DNA and inhibits genetic processes, including transcription and recombination. In Neurospora crassa, constitutive heterochromatin is characterized by trimethylation of lysine 9 on histone H3, hypoacetylation of histones, and DNA methylation. Here we explore whether the conserved histone demethylase, lysine-specific demethylase 1 (LSD1), regulates heterochromatin in Neurospora, and if so, how. Though LSD1 is implicated in heterochromatin regulation, its function is inconsistent across different systems; orthologs of LSD1 have been shown to either promote or antagonize heterochromatin expansion by removing H3K4me or H3K9me respectively. We identify three members of the Neurospora LSD complex (LSDC): LSD1, PHF1, and BDP-1, and strains deficient for any exhibit variable spreading of heterochromatin and establishment of new heterochromatin domains dispersed across the genome. Heterochromatin establishment outside of canonical domains in Neurospora share the unusual characteristic of DNA methylation-dependent H3K9me3; typically, H3K9me3 establishment is independent of DNA methylation. Consistent with this, the hyper-H3K9me3 phenotype of LSD1 knock-out strains is dependent on the presence of DNA methylation, as well as HCHC-mediated histone deacetylation, suggesting spreading is dependent on some feedback mechanism. Altogether, our results suggest LSD1 works in opposition to HCHC to maintain proper heterochromatin boundaries.

2021-07-21 | PXD017300 | Pride

A transcription factor based mechanism for mouse heterochromatin formation

2012-09-16 | GSE40086 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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