Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetic Regulation of Serine Biosynthesis by PHF8 During Neurogenesis

ABSTRACT: During neurodevelopment, progenitor proliferation is a highly orchestrated process, involving precise epigenetic modifications and immense metabolic demands. Yet, the intricate interplay between epigenetics and metabolism remains largely unexplored. To investigate this, we utilized neural stem cells to examine the role of PHF8, a histone demethylase whose mutations are linked to Siderius-Hamel syndrome, a rare neurodevelopmental disorder. Through an integrated multi- omics approach—combining transcriptomics, epigenomics, and metabolomics—we identify PHF8 as a key driver of the serine biosynthesis pathway, safeguarding the intracellular serine pool essential for neural progenitor proliferation. PHF8 fine- tunes chromatin accessibility at promoters of metabolic genes, ensuring their activation during development. Notably, loss of PHF8 not only disrupts amino acid metabolism and mTORC1 signaling, but also blocks autophagic flux, and impairs vesicle formation—ultimately stalling proliferation and triggering replicative defects and DNA damage. In vivo, PHF8 deficiency in mouse embryos halts neurogenesis, affecting progenitor expansion and neuron generation in the developing brain. Altogether, our work positions PHF8 as a pivotal molecular node linking chromatin dynamics, metabolic regulation, and neural development. These findings not only deepen our understanding of brain development but also open new avenues for exploring the epigenetic basis of metabolic and neurodevelopmental disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE296528 | GEO | 2025/12/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Epigenetic Regulation of Serine Biosynthesis by PHF8 During Neurogenesis [ChIP-Seq H3K9me3]

Project description:During neurodevelopment, progenitor proliferation is a highly orchestrated process, involving precise epigenetic modifications and immense metabolic demands. Yet, the intricate interplay between epigenetics and metabolism remains largely unexplored. To investigate this, we utilized neural stem cells to examine the role of PHF8, a histone demethylase whose mutations are linked to Siderius-Hamel syndrome, a rare neurodevelopmental disorder. Through an integrated multi- omics approach—combining transcriptomics, epigenomics, and metabolomics—we identify PHF8 as a key driver of the serine biosynthesis pathway, safeguarding the intracellular serine pool essential for neural progenitor proliferation. PHF8 fine- tunes chromatin accessibility at promoters of metabolic genes, ensuring their activation during development. Notably, loss of PHF8 not only disrupts amino acid metabolism and mTORC1 signaling, but also blocks autophagic flux, and impairs vesicle formation—ultimately stalling proliferation and triggering replicative defects and DNA damage. In vivo, PHF8 deficiency in mouse embryos halts neurogenesis, affecting progenitor expansion and neuron generation in the developing brain. Altogether, our work positions PHF8 as a pivotal molecular node linking chromatin dynamics, metabolic regulation, and neural development. These findings not only deepen our understanding of brain development but also open new avenues for exploring the epigenetic basis of metabolic and neurodevelopmental disorders.

2025-12-17 | GSE311637 | GEO

ChIP-seq experiment of PHF8 in Astrocytes differentiated from mouse NSCs

Project description:In this study we analyzed the contribution of PHF8 histone demethylase to astrocytes differentiation from mouse neural stem cells. We found that PHF8 depletion affects astocytes differentiation. Moreover, PHF8 is crucial for synaptogenesis in neurons/astrocytes cocultures. Genome wide analysis demonstrated that PHF8 controls the expression of critical astrogenic and synaptogenic genes by keeping low levels of H4K20me1 at promoters. PHF8 depletion induces aberrant astrocytes phenotype and caused a significant decrease in miniature excitatory postsynaptic currents (mEPSC) frequency and amplitude in neurons/astrocytes coclutures. These data reveal a new role of PHF8 in astrocyte differentiation and function, modulating neuronal synapse. Thus, lack of histone demethylase activity associated to PHF8 mutations might led to synapse disfunction that could directly impact into X-linked intellectual disabilities.

2021-06-14 | GSE141969 | GEO

Genome-wide identification of target genes for the histone demethylase Phf8 in the oligodendroglial cell line CG4 [Phf8OE]

Project description:To identify target genes of the histone demethylase Phf8 in oligodendroglial cells in a genome-wide and unbiased approach, RNA-sequencing studies were performed on CG4 cells transduced with control or Phf8-overexpressing retroviruses. Transduced, GFP-expressing cells underwent fluorescence-activated cell-sorting, were expanded and then differentiated for three days. Two biological replicates were used for each condition. Gene expression analysis revealed an increase in oligodendrocyte progenitor proliferation and a general decrease in cell differentiation.

2024-04-12 | GSE253878 | GEO

Endogenous Cell Type-Specific DISC1 Interactomes Reveal Protein Networks Associated to Neurodevelopmental Disorders

Project description:Disrupted in schizophrenia 1 (DISC1) has been implicated in contributing to a number of psychiatric diseases and neurodevelopmental phenotypes such as the proliferation and differentiation of neural progenitor cells. While there has been significant effort directed towards understanding the function of DISC1 through the determination of its protein-protein interactions within an in-vitro setting, endogenous interactions involving DISC1 within a cell-type specific setting relevant to neural development remain unclear.

2018-07-04 | PXD007103 | Pride

Analysis of transcriptional and epigentic changes induced by loss of Phf8 [RNA-seq]

Project description:Phf8 is a histone demethylase with links to human behavior. Here we have performed a transcriptional analysis of Phf8 knockout embryonic stem and neural projenitor cells in vitro along with an analysis of the prefrontal cortex and ventral striatum in vivo. Our results suggest that knockout of Phf8 is largely compensated for. However, we did observe a misregulation of serotonin receptors in the prefrontal cortex, which may have disease implications.

2017-02-14 | GSE90019 | GEO

RNA-seq data of PHF8 wild-type and PHF8 knockout TRAMP mouse

Project description:RNA-seq analysis were applied to elucidate the transcriptional differences of PHF8 wild-type and PHF8 knockout TRAMP mouse. A total of 2,092 differentially expressed genes (Fold Change > 2, or Fold Change＜0.5; FDR < 0.05) with 623 down- and 1469 up-regulated genes were identifed in Phf8-KO TRAMP mice.

2020-09-26 | GSE157621 | GEO

Epigenetic Regulation of Serine Biosynthesis by PHF8 During Neurogenesis

Project description:Epigenetic Regulation of Serine Biosynthesis by PHF8 During Neurogenesis

| PRJNA1259900 | ENA

APOC2 increase PHF8 binding on chromatin

Project description:We performed PHF8 ChIP-seq analysis of APOC2 overexpressed RKO cells and control cells to identify high-confident PHF8 regulated targets.

2021-05-07 | GSE114089 | GEO

The histone demethylase PHF8 is essential for cytoskeleton dynamics

Project description:PHF8 is a histone demethylase associated with X-linked mental retardation (XLMR). It has been described as a transcriptional coactivator involved in cell cycle progression, but its physiological role is still poorly understood. Here we show that PHF8 controls the expression of genes involved in cell adhesion and cytoskeleton organization such as RhoA, Rac1 and GSK3M-NM-2. A lack of PHF8 not only results in a cell cycle delay but also in a disorganized actin cytoskeleton and impaired cell adhesion. Our data demonstrate that PHF8 directly regulates the expression of these genes by demethylating H4K20me1 at promoters. Moreover, c-Myc transcription factor interacts with PHF8 and binds to the analyzed promoters, suggesting that c-Myc is involved on PHF8 recruitment to these promoters. Further analysis in the neuroblastoma cell line SH-SY5Y and in cortical neurons shows that depletion of PHF8 results in deficient neurite elongation. Overall, our results suggest that the mental retardation phenotype associated with loss of function of PHF8 could be due to abnormal neuronal connections as a result of alterations in cytoskeleton function. HeLa cells were transfected with either control or PHF8 siRNAs. Experiments were performed in biological triplicates. RNA were extracted and sujected to microarray analysis.

2012-07-31 | E-GEOD-38175 | biostudies-arrayexpress

RNA-seq data of 786-O cells transfected with control-sgRNA (Control) and PHF8-sgRNA (PHF8-KO)

Project description:RNA-seq analysis were applied to elucidate the transcriptional differences between 786-O cell lines transfected with control-sgRNA (Control) and PHF8-sgRNA (PHF8-KO). A total of 3575 differentially expressed genes (Fold Change > 2, or Fold Change＜0.5; FDR < 0.05) with 2097 down- and 1478 up-regulated genes were identified in PHF8-KO 786-O cells

2022-10-08 | GSE214183 | 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