Polycomb Repressor Complex2 and REST-associated histone deacetylases are independent pathways toward a mature neuronal phenotype
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE59442 | GEO | 2014/09/30
SECONDARY ACCESSION(S): PRJNA255330
REPOSITORIES: GEO
Similar Datasets
Project description:These experiments were designed to test the hypothesis that REST and Polycomb Repressor Complex 2 function cooperatively in undifferentiated ESCs. Our results show that H3K27me3-enriched genes show no de-repression in REST-/- ESCs, while REST target genes show significant de-repression. RNA-seq was performed and analyzed using two biological replicates for each genotype, WT (N6) and REST-/- (N8) mouse embryonic stem cells.
2014-09-30 | E-GEOD-59442 | biostudies-arrayexpress
Project description:These experiments were designed to test the hypothesis that REST and Polycomb Repressor Complex 2 function cooperatively in undifferentiated ESCs. Our results showed that a majority of REST-bound genomic regions were not associated with H3K27me3 enrichment and loss of H3K27me3 enrichment was not a general observation in REST -/- ESCs. These results support the conclusion that REST and PRC2 function independently in ESCs and similarly contribute to maintaing a transcriptionally poised state through antagonism of H3K4me3. Examination of REST-bound regions in undifferentiated mouse embryonic stem cells (ESC), and a comparison of H3K27me3 distribution between WT and REST-/- ESCs.
2014-09-30 | E-GEOD-48320 | biostudies-arrayexpress
Project description:These experiments were designed to test the hypothesis that REST and Polycomb Repressor Complex 2 function cooperatively in undifferentiated ESCs. Our results showed that a majority of REST-bound genomic regions were not associated with H3K27me3 enrichment and loss of H3K27me3 enrichment was not a general observation in REST -/- ESCs. These results support the conclusion that REST and PRC2 function independently in ESCs and similarly contribute to maintaing a transcriptionally poised state through antagonism of H3K4me3.
2014-09-30 | GSE48320 | GEO
Project description:Neural differentiation of embryonic stem cells (ESCs) requires coordinated repression of the pluripotency regulatory programme and reciprocal activation of the neurogenic regulatory programme. Upon neural induction, ESCs rapidly repress expression of pluripotency genes followed by staged activation of neural progenitor and differentiated neuronal and glial genes. The transcriptional factors that underlie pluripotency are partially characterized, whereas those underlying neural induction are much less explored, and the factors that coordinate these two developmental programs are completely unknown. One transcription factor, REST (RE1 silencing transcription factor), has been linked with terminal differentiation of neural progenitors, and more recently and controversially, with control of pluripotency. Here, we show that in the absence of REST, coordination of pluripotency and neural induction is lost and there is a resultant delay in repression of pluripotency genes and a precocious activation of both neural progenitor and differentiated neuronal and glial genes. Further, we show that REST is not required for production of radial glia-like progenitors but is required for their subsequent maintenance and differentiation into neurons, oligodendrocytes and astrocytes. We propose that REST acts as a regulatory hub that coordinates timely repression of pluripotency with neural induction and neural differentiation. We have investigated the role of REST in the coupling of pluripotency and neural induction and neurogenesis using Rest-null mouse ESCs (mESCs) in conjunction with a novel mESC neural differentiation protocol. Differential expression between Rest-null ESCs and controls was tested using Illumina Mouse Ref-8 v2 BeadArray technology. Three replicates were used for Rest-null and three for control. Data analysis was performed using Bioconductor libraries beadarray and limma.
2011-12-08 | E-GEOD-34244 | biostudies-arrayexpress
Project description:Neural differentiation of embryonic stem cells (ESCs) requires coordinated repression of the pluripotency regulatory programme and reciprocal activation of the neurogenic regulatory programme. Upon neural induction, ESCs rapidly repress expression of pluripotency genes followed by staged activation of neural progenitor and differentiated neuronal and glial genes. The transcriptional factors that underlie pluripotency are partially characterized, whereas those underlying neural induction are much less explored, and the factors that coordinate these two developmental programs are completely unknown. One transcription factor, REST (RE1 silencing transcription factor), has been linked with terminal differentiation of neural progenitors, and more recently and controversially, with control of pluripotency. Here, we show that in the absence of REST, coordination of pluripotency and neural induction is lost and there is a resultant delay in repression of pluripotency genes and a precocious activation of both neural progenitor and differentiated neuronal and glial genes. Further, we show that REST is not required for production of radial glia-like progenitors but is required for their subsequent maintenance and differentiation into neurons, oligodendrocytes and astrocytes. We propose that REST acts as a regulatory hub that coordinates timely repression of pluripotency with neural induction and neural differentiation.
2011-12-08 | GSE34244 | GEO
Project description:Genome-wide analysis of REST and Polycomb binding in Rest-/- and Eed-/- mouse embryonic stem (mES) cells showed that Rest was required for PRC1 recruitment to a subset of Polycomb regulated neuronal genes. Furthermore, we found that PRC1 can be recruited to Rest binding sites independently of CpG islands and the H3K27Me3 mark., and that PRC2 was frequently increased around Rest binding sites located in CpG-rich regions in the Rest2/2 mES cells. Published here: PLoS Genet 8(3): e1002494. doi:10.1371/journal.pgen.1002494
2013-06-20 | GSE48122 | GEO
Project description:Genome-wide analysis of REST and Polycomb binding in Rest-/- and Eed-/- mouse embryonic stem (mES) cells showed that Rest was required for PRC1 recruitment to a subset of Polycomb regulated neuronal genes. Furthermore, we found that PRC1 can be recruited to Rest binding sites independently of CpG islands and the H3K27Me3 mark., and that PRC2 was frequently increased around Rest binding sites located in CpG-rich regions in the Rest2/2 mES cells. Published here: PLoS Genet 8(3): e1002494. doi:10.1371/journal.pgen.1002494 Examination of REST and Polycomb binding in Rest-/-, Eed-/-, and wt mES cells using ChIP-sequencing. Submitter cannot locate the raw data for GSM1169003, GSM1169004, GSM1169011, GSM1169012, GSM1169015, and GSM1169016.
2013-06-20 | E-GEOD-48122 | biostudies-arrayexpress
Project description:Uterine Leiomyomas (UL) are benign tumors that arise in the myometrium of the uterus. The standard treatment option for UL is hysterectomy but hormonal treatment options are emerging in the field. However, since the pathogenesis of UL is poorly understood, hallmarks that predict long-term efficacy and safety of these treatment options remain largely undefined. We have reported previously that REST/NRSF target genes are aberrantly expressed due to the near ubiquitous loss of this epigenetic repressor in UL tumors. We show that ablation of Rest in the mouse uterus leads to UL phenotype and altered response to steroid hormones estrogen and progesterone. Additionally, we demonstrate that a large number of REST target genes dysregulated in UL as well as in Rest cKO mice, are also targets of progesterone receptor (PR). Importantly, we identify a direct interaction between REST and PR in the healthy myometrium. Rest cKO mouse model phenocopies human UL, including gene expression profiles of UL as well as tumor formation in the myometrium. Our findings emphasize the critical role loss of REST plays in disease pathogenesis and the altered response to steroid hormones seen in UL.
2022-10-12 | GSE178140 | GEO
Project description:Uterine Leiomyomas (UL) are benign tumors that arise in the myometrium of the uterus. The standard treatment option for UL is hysterectomy but hormonal treatment options are emerging in the field. However, since the pathogenesis of UL is poorly understood, hallmarks that predict long-term efficacy and safety of these treatment options remain largely undefined. We have reported previously that REST/NRSF target genes are aberrantly expressed due to the near ubiquitous loss of this epigenetic repressor in UL tumors. We show that ablation of Rest in the mouse uterus leads to UL phenotype and altered response to steroid hormones estrogen and progesterone. Additionally, we demonstrate that a large number of REST target genes dysregulated in UL as well as in Rest cKO mice, are also targets of progesterone receptor (PR). Importantly, we identify a direct interaction between REST and PR in the healthy myometrium. Rest cKO mouse model phenocopies human UL, including gene expression profiles of UL as well as tumor formation in the myometrium. Our findings emphasize the critical role loss of REST plays in disease pathogenesis and the altered response to steroid hormones seen in UL.
2022-10-12 | GSE178086 | GEO
Project description:Genetic evidence indicates disrupted epigenetic regulation as a major risk factor for psychiatric disorders, but the molecular mechanisms that drive this association are undetermined. EHMT1 is an epigenetic repressor that is causal for Kleefstra Syndrome (KS), a neurodevelopmental disorder (NDD) leading to ID, and is associated with schizophrenia. Here, we show that reduced EHMT1 activity decreases NRSF/REST protein leading to abnormal neuronal gene expression and progression of neurodevelopment in human iPSC. We further show that EHMT1 regulates NRSF/REST indirectly via repression of miRNA leading to aberrant neuronal gene regulation and neurodevelopment timing. Expression of a NRSF/REST mRNA that lacks the miRNA-binding sites restores neuronal gene regulation to EHMT1 deficient cells. Importantly, the EHMT1-regulated miRNA gene set with elevated expression is enriched for NRSF/REST regulators with an association for ID and schizophrenia. This reveals a molecular interaction between H3K9 dimethylation and NSRF/REST contributing to the aetiology of psychiatric disorders.
2023-05-01 | E-MTAB-10480 | biostudies-arrayexpress