Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Histone bivalency regulates the timing of cerebellar granule cell development in vivo [RNA-seq]

ABSTRACT: Developing neurons undergo a progression of morphological and gene expression changes as they transition from neuronal progenitors to mature, multipolar neurons. Here we use RNA-seq and ChIP-seq to analyze how chromatin modifications control gene expression in a specific type of CNS neuron, the mouse cerebellar granule cell (GC). We find that in proliferating GC progenitors, H3K4me3/H3K27me3 bivalency is common at neuronal genes and undergoes dynamic changes that correlate with gene expression during migration and circuit formation. Inhibiting H3K27 methyltransferases EZH1 and EZH2 in vitro and in organotypic cerebellar slices dramatically altered the expression of bivalent genes and induced the downregulation of migration-related genes and upregulation of synaptic genes, inhibited glial-guided migration and accelerated dendrite formation. These data show that histone bivalency is required to regulate the timing of the progression from progenitor cells to mature neurons.

ORGANISM(S): Mus musculus

PROVIDER: GSE223486 | GEO | 2023/02/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Histone bivalency regulates the timing of cerebellar granule cell development in vivo [ChIP-seq]

Project description:Developing neurons undergo a progression of morphological and gene expression changes as they transition from neuronal progenitors to mature, multipolar neurons. Here we use RNA-seq and ChIP-seq to analyze how chromatin modifications control gene expression in a specific type of CNS neuron, the mouse cerebellar granule cell (GC). We find that in proliferating GC progenitors, H3K4me3/H3K27me3 bivalency is common at neuronal genes and undergoes dynamic changes that correlate with gene expression during migration and circuit formation. Inhibiting H3K27 methyltransferases EZH1 and EZH2 in vitro and in organotypic cerebellar slices dramatically altered the expression of bivalent genes and induced the downregulation of migration-related genes and upregulation of synaptic genes, inhibited glial-guided migration and accelerated dendrite formation. These data show that histone bivalency is required to regulate the timing of the progression from progenitor cells to mature neurons.

2023-02-06 | GSE223485 | GEO

Tracking bivalency through early mouse differentiation

Project description:Nucleosomes, composed of DNA and histone proteins, represent the fundamental repeating unit of the eukaryotic genome; posttranslational modifications of these histone proteins influence the activity of the associated genomic regions to regulate cell identity. Traditionally, trimethylation of histone H3K4 (H3K4me3) is associated with transcriptional initiation, whereas trimethylation of H3K27 (H3K27me3) is transcriptionally repressive. The apparent juxtaposition of these opposing marks, termed “bivalent domains”, was proposed to specifically demarcate of small set transcriptionally-poised lineage-commitment genes that resolve to one constituent modification through differentiation, thereby determining transcriptional status. Since then, many thousands of studies have canonized the bivalency model as a chromatin hallmark of development in many cell types. However, these conclusions are largely based on chromatin immunoprecipitations (ChIP) with significant methodological problems hampering their interpretation. Absent direct quantitative measurements, it has been difficult to evaluate the strength of the bivalency model. Here, we present reICeChIP, a calibrated sequential ChIP method to quantitatively measure H3K4me3/H3K27me3 bivalency genome-wide, addressing the limitations of prior measurements. With reICeChIP, we profile bivalency through the differentiation paradigm that first established this model: from naïve mouse embryonic stem cells (mESCs) into neuronal progenitor cells (NPCs). Our results cast doubt on every aspect of the bivalency model; in this context, we find that bivalency is widespread, does not resolve with differentiation, and is neither sensitive nor specific for identifying poised developmental genes or gene expression status more broadly. Our findings caution against interpreting bivalent domains as specific markers of developmentally poised genes.

2021-09-10 | GSE183155 | GEO

ZEB1 represses neural differentiation and cooperates with CTBP2 to dynamically regulate cell migration during neocortex development [RNA-seq]

Project description:Zinc finger E-box binding homeobox 1 (Zeb1) is a key regulator of epithelial-mesenchymal transition and cancer metastasis. Mutation of ZEB1 is associated with human diseases and defective brain development. Here we show that down-regulation of Zeb1 expression in the embryonic cortical neural progenitor cells (NPCs) is necessary for proper neuronal differentiation and migration. Overexpression of Zeb1 during neuronal differentiation when its expression normally declines blocks NPC lineage progression and disrupts multipolar-to-bipolar transition of differentiating neurons, leading to severe migration defects and subcortical heterotopia bands at the postnatal stage. We found that ZEB1 regulates a cohort of genes involved in cell differentiation and migration, including Neurod1 and Pard6b. Interestingly, interaction between ZEB1 and CTBP2 in the embryonic cerebral cortex is required for ZEB1 to elicit its effect on multipolar-to-bipolar transition but not its suppression of Neurod1. These findings provide insights into understanding the complexity of transcriptional regulation during neuronal differentiation.

2019-05-21 | GSE127912 | GEO

ZEB1 represses neural differentiation and cooperates with CTBP2 to dynamically regulate cell migration during neocortex development [ChIP-seq]

2019-05-21 | GSE127913 | GEO

FACS microarray analysis of radially migrating cortical neurons

Project description:During the developmental formation of 6-layered neocortical structure of mammalian cerebral cortex, newborn excitatory neurons depart the ventricular zone and migrate toward the pial surface. At a middle stage of cortical development, newly differentiated postmitotic neurons adopt a multipolar shape (MP), and exhibit a random non-directional migration in the intermediate zone (multipolar migration). When these neurons pass through the subplate layer (SP), they convert to a bipolar shape (BP), and then migrate radially toward the pial surface (locomotion). In order to elucidate the molecular mechanisms of such neuronal migration, we performed a gene expression profiling of newborn excitatory neurons during their migration processes. After in utero electroporation of GFP expressing plasmid into E14 mouse cortex, GFP-positive cells were collected using FACS sorting method after one, two, or three days of electroporation. RNAs of collected GFP-positive cells at each day were purified and applied to microarray analyses. gene-ontology and pathway analyses revealed that genes encoding synaptic proteins, receptors and ECM-related proteins were up-regulated as the migration proceeds. On the other hand, genes encoding cell cycle regulation and immune-related proteins were down-regulated. We will discuss the relationship between the migration mode and the transition of the gene expression.

2017-08-23 | GSE102911 | GEO

Generation of advanced cerebellar organoids for neurogenesis and neuronal network development

Project description:Neurons within the cerebellum form temporal-spatial connections through the cerebellum, and the entire brain. Organoid models provide an opportunity to model the early differentiation of the developing human cerebellum, which is difficult to study in vivo, and affords the opportunity to study neurodegenerative and neurodevelopmental diseases of the cerebellum. Previous cerebellar organoid models focused on early neuron generation and single cell activity. Here, we modify previous protocols to generate more mature cerebellar organoids that allow for the establishment of several classes of mature neurons during cerebellar differentiation and development, including the establishment of neural networks during whole organoid maturation. This will provide a means to study the generation of several more mature cerebellar cell types, including Purkinje cells, granule cells, interneurons expression as well as neuronal communication for biomedical, clinical, and pharmaceutical application.

2023-07-20 | GSE237855 | GEO

Cdc42 phosphorylation study - Cdc42 Regulates Neuronal Polarity during Cerebellar Axon Formation and Glial-Guided Migration

Project description:Govek et al. demonstrate conditional loss of Cdc42 in cerebellar granule cell progenitors (GCPs) perturbs GCP polarity and impairs axon patterning, glial-guided migration, and cerebellar foliation. Phospho-proteomic analysis identified polarity and cytoskeletal proteins as affected targets in Cdc42 deficient GCPs.

2018-10-22 | PXD008148 | Pride

Regulation of Tlx3 by Pax6 is required for the restricted expression of ChrnÎ±3 in Cerebellar Granule Neuron progenitors during development

Project description:Homeobox gene Tlx3 is known to promote glutamatergic differentiation and is expressed in post-mitotic neurons of CNS. Contrary to this here, we discovered that Tlx3 is expressed in the proliferating progenitors of the external granule layer in the cerebellum, and examined factors that regulate this expression. Using Pax6-/-Sey mouse model and molecular interaction studies we demonstrate Pax6 is a key activator of Tlx3 specifically in cerebellum, and induces its expression starting at embryonic day (E)15. By Postnatal day (PN)7, Tlx3 is expressed in a highly restricted manner in the cerebellar granule neurons of the posterior cerebellar lobes, where it is required for the restricted expression of nicotinic cholinergic receptor-Î±3 subunit (ChrnÎ±3) and other genes involved in formation of synaptic connections and neuronal migration. These results demonstrate a novel role for Tlx3 and indicate that Pax6-Tlx3 expression and interaction is part of a region specific regulatory network in cerebellum and its deregulation during development could possibly lead to Autistic spectral disorders (ASD) Anterior and posterior lobes of PN7 mouse cerebellum were isolated separately and differentially expressed genes were identified.

2016-06-30 | E-GEOD-82097 | biostudies-arrayexpress

RNA-seq of fluorescence activated cell sorting purified mature olfactory sensory neurons and progenitor cells

Project description:This experiment studies the gene expression in the mature olfactory sensory neurons and the intermidiate neuronal progenitors in the olfactory epithelia during the critical period. Mature olfactory sensory neurons from OMP-GFP mice and intermediate neuronal progenitors in the olfactory epithelia from Neurog1-GFP mice were FACS purified. PolyA RNA profiles at P2, P3, P7, P9, and P16 were generated by RNA-Seq.

2022-08-29 | GSE147460 | GEO

Role of small RNA in post-natal olfactory bulb neurogenesis in mouse

Project description:We performed deep-sequencing analysis of small RNA extracted from neuronal progenitors at different developmental stages. The RNA samples were extracted from microdissected tissues of dorsal or lateral sub-ventricular zone (SVZ) (to analyze the immature progenitor pools), of rostral migration stream (RMS) (to analyze the migrating neuroblasts) or of olfactory bulbs (OB) (to analyze both immature and mature neurons). These tissues were dissected from animals at variable ages: P1 and P6 for SVZ samples, P15 and P28 for RMS and OB samples. Expression profile of microRNA in time and space along post-natal neurogenesis

2014-08-28 | E-GEOD-60817 | 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