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The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE122174 | GEO | 2019/12/31

REPOSITORIES: GEO

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The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation [RNA-Seq]

Project description:Snf2l and the closely related protein, Snf2h, play a critical role in embryonic and post-natal brain development. Murine models lacking functional Snf2h or Snf2l point to complementary activities of these remodelers; Snf2h cKO mice present with a significantly reduced cerebellum, while Snf2l Ex6DEL cerebella are larger than their wild-type counterparts. Granule neuron progenitors (GNPs) isolated from Ex6DEL cerebella display delayed cell cycle exit and hindered terminal differentiation compared to wild-type littermates. Moreover, loss of Snf2l activity results in widespread transcriptome shifts which underlie the Ex6DEL GNP differentiation phenotype. In particular, key transcription factors (TFs) are differentially expressed without Snf2l remodelling activity. We confirm that ERK pathway activation is misregulated in Ex6DEL GNPs, possibly in response to elevated fibroblast growth factor 8 (Fgf8) expression in these cultures. We find that Snf2l activity maintains the chromatin landscape throughout GNP differentiation, as Ex6DEL cultures have a global increase in chromatin accessibility. We suggest that Snf2l-mediated chromatin condensation is responsible for proper regulation of gene expression programs in GNP differentiation.

2019-12-31 | GSE122173 | GEO

The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation [ATAC-Seq]

2019-12-31 | GSE122172 | GEO

The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation

Project description:The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation

| PRJNA503865 | ENA

The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation [RNA-Seq]

Project description:The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation [RNA-Seq]

| PRJNA503868 | ENA

The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation [ATAC-Seq]

Project description:The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation [ATAC-Seq]

| PRJNA503869 | ENA

Impaired SNF2L Chromatin Remodeling Prolongs Accessibility at Promoters Enriched for Fos/Jun Binding Sites and Delays Granule Neuron Differentiation.

Project description:Chromatin remodeling proteins utilize the energy from ATP hydrolysis to mobilize nucleosomes often creating accessibility for transcription factors within gene regulatory elements. Aberrant chromatin remodeling has diverse effects on neuroprogenitor homeostasis altering progenitor competence, proliferation, survival, or cell fate. Previous work has shown that inactivation of the ISWI genes, Smarca5 (encoding Snf2h) and Smarca1 (encoding Snf2l) have dramatic effects on brain development. Smarca5 conditional knockout mice have reduced progenitor expansion and severe forebrain hypoplasia, with a similar effect on the postnatal growth of the cerebellum. In contrast, Smarca1 mutants exhibited enlarged forebrains with delayed progenitor differentiation and increased neuronal output. Here, we utilized cerebellar granule neuron precursor (GNP) cultures from Smarca1 mutant mice (Ex6DEL) to explore the requirement for Snf2l on progenitor homeostasis. The Ex6DEL GNPs showed delayed differentiation upon plating that was not attributed to changes in the Sonic Hedgehog pathway but was associated with overexpression of numerous positive effectors of proliferation, including targets of Wnt activation. Transcriptome analysis identified increased expression of Fosb and Fosl2 while ATACseq experiments identified a large increase in chromatin accessibility at promoters many enriched for Fos/Jun binding sites. Nonetheless, the elevated proliferation index was transient and the Ex6DEL cultures initiated differentiation with a high concordance in gene expression changes to the wild type cultures. Genes specific to Ex6DEL differentiation were associated with an increased activation of the ERK signaling pathway. Taken together, this data provides the first indication of how Smarca1 mutations alter progenitor cell homeostasis and contribute to changes in brain size.

| S-EPMC8290069 | biostudies-literature

Bidirectional changes in postmitotic H3K27me3 distributions underlie cerebellar granule neuron maturation dynamics

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

2022-10-11 | GSE212441 | GEO

Norrin-dependent gene expression in murine cerebellar granule neuron progenitors and Patched medulloblastoma

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

2016-10-12 | GSE81964 | GEO

Directed differentiation of human hindbrain neuroepithelial stem cells recapitulates cerebellar granule neurogenesis.

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

2023-05-29 | GSE233339 | GEO

Cerebellar Granule Neuron Temporal-NFI Microarray Data

Project description:Dendrite and synapse development are critical for establishing appropriate neuronal circuits, and disrupted timing of these events can alter connectivity leading to disordered neural function. In early postnatal development of cerebellar granule neurons (CGNs), the expression of many genes is temporally regulated. Further, NFI (Nuclear Factor I) proteins have been shown to play important roles in the regulation of gene expression in developing CGNs. To identify NFI-regulated genome-wide targets involved in late maturation of mouse CGNs, we performed two groups of microarray expression analysis: (1) temporal expression arrays using 1.5 and 6 day cultures of mouse CGNs representing immature and more mature CGNs, respectively, which identified 844 Temporal-Up or Down genes; and (2) NFI-regulated genes in 6 day CGN cultures that were infected at the time of plating with lentiviral vectors expressing either NFI dominant repressor (NFI-EnR) or EnR control protein. This identified 686 NFI-Up (NFI-EnR down-regulated) or NFI-Down (NFI-EnR up-regulated) genes. Overlap analysis identified 212 temporal genes that were regulated by NFI. These results indicated that NFI plays a pivotal role in the regulation of late CGN maturation. For temporal arrays, mouse CGN progenitors were purified from P6 mouse cerebellum and cultured for either 1.5 or 6 days. Three biological replicates were analyzed for each time point. For NFI arrays, CGN progenitors from P6 mice were transduced upon plating with either NFI-EnR or EnR control lentivirus and cultured 6 days. Four pairs of biological replicates were performed.

2012-11-07 | E-GEOD-42018 | biostudies-arrayexpress

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