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Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

ABSTRACT: We report that NEUROD1 mainly localises at distal intergenic and intronic regions in vitro, and colocalises with FOXG1.

ORGANISM(S): Mus musculus

PROVIDER: GSE189115 | GEO | 2023/01/09

REPOSITORIES: GEO

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Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

Project description:We report that FOXG1 localises at promoter, distal intergenic and intronic regions in vitro.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.

2023-01-09 | GSE189111 | GEO

Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

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.

2023-01-09 | GSE189110 | GEO

Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

Project description: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.

2023-01-09 | GSE189118 | GEO

Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

2023-01-09 | GSE189116 | GEO

Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

2023-01-09 | GSE189114 | GEO

Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

2023-01-09 | GSE189113 | GEO

Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

Project description:The integrative and multi-omics view of changes upon FOXG1 reduction reveals an unprecedented multimodality of FOXG1 functions converging on neuronal maturation, fueling novel therapeutic options based on epigenetic drugs to alleviate, at least in part, neuronal dysfunctions. This RNA-seq dataset is part of tis multimodal invetigation of FOXG1 functions.

2023-01-09 | GSE189117 | GEO

FoxG1 function in hippocampus

Project description:The forkhead box transcription factor FoxG1 is known to influence forebrain development by determining regional brain specification as well as by regulating expansion of neuronal progenitors and timing of their differentiation. In the adult brain, FoxG1 is expressed in cortex and hippocampus. In the latter it is involved in postnatal neurogenesis in the dentate gyrus by influencing maintenance of the progenitor pool as well as survival and maturation of postmitotic neurons. In humans, haploinsufficiency of FoxG1 causes the congenital version of the Rett syndrome, a progressive neurologic developmental disorder. We use FoxG1 mutant mice to screen for global changes in mRNA expression after partial loss of FoxG1 protein in hippocampi of six week-old mice. Data analysis points to a specific function for FoxG1 in adult hippocampus besides its known involvement in dentate gyrus neurogenesis. We analyse transcriptional changes in the different CA-fields and show that especially the CA-1 field is influenced by lack of FOXG1 protein. Furthermore, data analysis shows altered expression of genes that have also been implicated in the classical form of the Rett syndrome and other autism spectrum disorders.

2019-10-22 | GSE106801 | GEO

Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-01-09 | GSE189119 | GEO

Next-generation sequencing facilitates quantitative analysis of the transcriptomes of FOXG1 100% dosage, FOXG1 60% dosage, FOXG1 30% dosage, and FOXG1 0% dosage GABA interneurons derived from human embryonic stem cells

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

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