The lincRNA Pantr1 mediates site-specific chromatin binding of FOXG1 in hippocampal neurons
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ABSTRACT:
PROVIDER: PRJNA1139123 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29927567.fastq.gz | Fastqsanger.gz | |||
| SRR29927568.fastq.gz | Fastqsanger.gz | |||
| SRR29927569.fastq.gz | Fastqsanger.gz | |||
| SRR29927570.fastq.gz | Fastqsanger.gz | |||
| SRR29927571.fastq.gz | Fastqsanger.gz |
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Project description:Derailed gene expression programs within the developing nervous system, encompassing both transcriptional and posttranscriptional processes, are implicated in diverse neurodevelopmental diseases. One of those debilitating diseases, the FOXG1-syndrome, lacks full understanding of the mechanistic role of its eponymous gene product, FOXG1. While it is known that FOXG1 acts in part at the chromatin by binding to regulative regions, it is unclear what factors control its presence at specific sites. Long non-coding RNAs (lncRNAs) can mediate site-directed transcription factor binding, but their potential role in FOXG1-syndrome has not been described. Here, we show that the lncRNA Pantr1 mediates site specific binding of FOXG1 using FOXG1 ChIP sequencing upon Pantr1 knockdown.
2025-05-21 | GSE272852 | GEO
Project description:This study instigates the role of the long non-coding RNA Pantr1 (or Brn1a) in the context of nervous system development and in the neurodevelopmental disorder Foxg1-related syndrome. We report a high-throughput single-end RNA sequencing experiment in hippocampal neurons cultured in vitro in mouse. We performed the knockdown of Purb, Pantr1 and Foxg1 in hippocampal neurons cultured in vitro to 7 days and performed RNA-seq analysis.
2025-05-21 | GSE172220 | GEO
Project description:FOXG1 syndrome is a developmental encephalopathy with a high phenotypic variability, which results from FOXG1 mutations. However, the upstream transcriptional regulation of Foxg1 expression remains unclear. Here we report that both deficiency and overexpression of Men1 (protein: menin, a pathogenic gene of MEN1 syndrome) result in autism-like behaviors, including social defects, increased repetitive behaviors and cognition impairments. We employed multifaceted transcriptome analyses and found that Foxg1 signaling is mostly altered in Men1 deficiency mice, through its regulation over Alpha Thalassemia/Mental Retardation Syndrome X-Linked (Atrx) factor. Atrx recruits menin to bind to the transcriptional start region of Foxg1 and mediates the regulation of Foxg1 expression by H3K4me3 modification. Notably, the described changes in menin deficient mice were rescued by over-expression of Foxg1, leading to normalized spine growth and hippocampal synaptic plasticity. Collectively, these results indicate a putative role of menin in maintaining Foxg1 expression, and menin signaling may serve as Foxg1-related encephalopathy therapeutic targets.
2024-07-03 | GSE261274 | GEO
Project description:Derailed gene expression programs within the developing nervous system, encompassing both transcriptional and posttranscriptional processes, can cause diverse neurodevelopmental diseases (NDD). The NDD FOXG1-syndrome lacks full understanding of the mechanistic role of its eponymous gene product. While it is known that FOXG1 acts in part at the chromatin by binding to regulative regions, it is unclear what factors control its presence at specific sites. Long non-coding RNAs (lncRNAs) can mediate site-directed transcription factor binding, but their potential role in FOXG1-syndrome has not been described. Here, we show that FOXG1 localisation is regulated at selected loci through the lncRNA Pantr1.
We identified FOXG1 as an upstream transcriptional activator of Pantr1 in human and mice. Further, we discovered that FOXG1 has the ability to associate with RNAs. Both, transcriptional regulation of Pantr1 by FOXG1 and association of both partners, build up a regulative network that impacts the localisation of FOXG1 at selected genomic loci. Specifically, Pantr1 facilitates cooperative presence of FOXG1/NEUROD1 at specific sites, and Pantr1 reduction leads to redistribution of FOXG1 to comparably more generic binding sites. The rescue of impaired dendritic outgrowth upon FOXG1 reduction by simultaneous overexpression of Pantr1 underlines the importance of the FOXG1/Pantr1 regulative network.
2025-04-15 | MSV000097630 | MassIVE
Project description:Derailed gene expression programs within the developing nervous system, encompassing both transcriptional and posttranscriptional processes, can cause diverse neurodevelopmental diseases (NDD). The NDD FOXG1-syndrome lacks full understanding of the mechanistic role of its eponymous gene product. While it is known that FOXG1 acts in part at the chromatin by binding to regulative regions, it is unclear what factors control its presence at specific sites. Long non-coding RNAs (lncRNAs) can mediate site-directed transcription factor binding, but their potential role in FOXG1-syndrome has not been described. Here, we show that FOXG1 localisation is regulated at selected loci through the lncRNA Pantr1.
We identified FOXG1 as an upstream transcriptional activator of Pantr1 in human and mice. Further, we discovered that FOXG1 has the ability to associate with RNAs. Both, transcriptional regulation of Pantr1 by FOXG1 and association of both partners, build up a regulative network that impacts the localisation of FOXG1 at selected genomic loci. Specifically, Pantr1 facilitates cooperative presence of FOXG1/NEUROD1 at specific sites, and Pantr1 reduction leads to redistribution of FOXG1 to comparably more generic binding sites. The rescue of impaired dendritic outgrowth upon FOXG1 reduction by simultaneous overexpression of Pantr1 underlines the importance of the FOXG1/Pantr1 regulative network.
2025-04-15 | MSV000097629 | MassIVE
Project description:We report that the two adult neurogenic niches of the mammalian brain – the dentate gyrus of the hippocampal formation and the subependymal zone of the lateral ventricles - displayed differential vulnerability to increased FoxG1 dosage: high FoxG1 levels severely compromised survival and glutamatergic dentate granule neuron fate acquisition in the hippocampal neurogenic niche, but left neurogenesis of GABAergic neurons in the subependymal zone / olfactory bulb system unaffected. Comparative transcriptomic analyses revealed a significantly higher expression of the apoptosis-linked nuclear receptor Nr4a1 in FoxG1-overexpressing hippocampal neural precursors. Our results reveal differential vulnerability of neuronal subtypes to increased FoxG1 dosage and suggest that activity of a FoxG1/Nr4a1 axis contributes to such subtype-specific response.
2022-03-22 | GSE185315 | GEO
Project description:Rett syndrome is a complex neurodevelopmental disorder that is mainly caused by mutations in MECP2. However, mutations in FOXG1 cause a less frequent non-congenital form called atypical Rett syndrome. FOXG1 is a key transcription factor implicated in forebrain development, where it maintains the balance between progenitor proliferation and neuronal differentiation. Using SILAC based quantitative proteomics and genome-wide small RNA sequencing, we identified that FOXG1 interacts with the ATP-dependent RNA helicase, DDX5/p68 and controls the biogenesis of miRNAs. Both, FOXG1 and DDX5 bind to the miR200b/a/429 primary transcript and associate with the microprocessor complex, whereby DDX5 recruits FOXG1 to DROSHA. In vivo and in vitro experiments show that both FOXG1 and DDX5 are necessary for effective maturation of miR200b/a/429. RNAseq analyses of Foxg1-heterozygote hippocampi and miR200b/a/429 overexpressing Neuro-2a cells revealed that the cAMP-dependent protein kinase type II-beta regulatory subunit (PRKAR2B) is a target of miR200 in neural cells. Since it is known that PRKAR2B inhibits postsynaptic functions by attenuating protein kinase A (PKA) activity, increased PRKAR2B levels may contribute to neuronal dysfunctions in FOXG1 Rett syndrome.
2019-11-11 | PXD007040 | Pride
Project description:The role of the lincRNA Pantr1 during the development of the neurons in the FOXG1 syndrome mouse model
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Project description:Next-generation sequencing facilitates quantitative analysis of the transcriptomes of FOXG1 100% dosage GABA interneurons, FOXG1 60% dosage GABA interneurons, FOXG1 30% dosage GABA interneurons, and FOXG1 0% dosage GABA interneurons derived from human embryonic stem cells. We report a genetic manipulation system that enable precise dosage control of FOXG1 protein in human pluripotent stem cells (hPSCs). Using this system, we explored how the various reduced dosage affect human ventrol GABA interneuron development. We employed RNA seq on hPSC-derived GABA interneurons (day 60) to invest the expression pattern under different FOXG1 dosage conditions. RNA-Seq on GABA interneurons (Day 60) indicates that compared to the FOXG1 100% group, variable insufficiency of FOXG1 produces more than 1000 differently expressed genes (DEGs), and more DEGs in the group with less FOXG1 dosage. Heat map on Pearson Correlation indicates that groups with more discriminated FOXG1 exhibit much weaker correlation. Venn diagram reveals that each group has a set of distinct DEGs, suggesting that each FOXG1 protein dosage could results in different expression pattern during differentiation. The DEGs can be divided into two clusters, with one showing dosage-dependent regulation by FOXG1 and the other one typical binary. Key regulatory genes for GABA interneuron induction (NKX2-1, NKX6-2, GAD1, etc.) and for functional GABAergic-specific synapse formation (GABBR1, GABRA1, GABRB1, GABRG1, GABRQ, SHANK1, etc.) are down regulated along with reduction of FOXG1 protein.
2018-09-18 | GSE120079 | GEO
Project description:As part of our multimodal investigation fo FOXG1 functions at the chromatin, we report that there are both increase and decrease in chromatin accessibility upon reduced levels of FOXG1 in pirmary hippocampal neurons. The data presented in this study enlighten for the first time in a comprehensive manner diverse and multi-modal functions of FOXG1 at the chromatin level in mature neurons. Despite FOXG1 being recognized as a key transcription factor for telencephalic development and neuronal function, insights into the mechanism underlying transcriptional regulation are sparse. We here show that (i) FOXG1 acts both as repressor and activator, (ii) localizes predominantly to enhancer regions, (iii) alters the epigenetic landscape, (iv) affects directly HDAC functions, and (v) acts in concert with NEUROD1 to instruct transcriptional programs necessary for axono- and synaptogenesis.
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