Mecp2 fine-tunes quiescence exit by targeting nuclear receptors [RNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE227723 | GEO | 2024/04/26
REPOSITORIES: GEO
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Project description:To identify the Mecp2-dependent transcriptome genome-wide during the very early stage of liver regeneration, we mapped the binding landscape of Mecp2 in control and MeCP2-KO livers before and after PHx using ChIP-seq. we mapped the binding landscape of Mecp2 in control livers before and after PHx by filtering out peaks identified in Mecp2-cKO livers. we identified a total of 14640 and 15350 Mecp2-binding genes before and after PHx in the Mecp2 control liver, respectively.
2024-04-26 | GSE227727 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-04-26 | GSE227728 | GEO
Project description:In budding yeast, the major regulator of the mitotic exit network (MEN) is Tem1, a GTPase, which is inhibited by the GTPase-activating protein (GAP), Bfa1/Bub2. Asymmetric Bfa1 localization to the bud-directed spindle pole body (SPB) during metaphase also controls mitotic exit, but the molecular mechanism and function of this localization are not well understood, particularly in unperturbed cells. We identified four novel Cdc5 target residues within the Bfa1 C-terminus: (452)S, (453)S, (454)S, and (559)S. A Bfa1 mutant in which all of these residues had been changed to alanine (Bfa1(4A)) persisted on both SPBs at anaphase and was hypo-phosphorylated, despite retaining its GAP activity for Tem1. A Bfa1 phospho-mimetic mutant in which all of these residues were switched to aspartate (Bfa1(4D)) always localized asymmetrically to the SPB. These observations demonstrate that asymmetric localization of Bfa1 is tightly linked to its Cdc5-dependent phosphorylation, but not to its GAP activity. Consistent with this, in kinase-defective cdc5-2 cells Bfa1 was not phosphorylated and localized to both SPBs, whereas Bfa1(4D) was asymmetrically localized. BFA1(4A) cells progressed through anaphase normally but displayed delayed mitotic exit in unperturbed cell cycles, while BFA1(4D) cells underwent mitotic exit with the same kinetics as wild-type cells. We suggest that Cdc5 induces the asymmetric distribution of Bfa1 to the bud-directed SPB independently of Bfa1 GAP activity at anaphase and that Bfa1 asymmetry fine-tunes the timing of MEN activation in unperturbed cell cycles.
| S-EPMC3257293 | biostudies-other
Project description:MECP2-R270X transgenic mice (TG) and MECP2-G273X TG mice were generated in the Zoghbi Lab. These mice express the respective truncated form of MeCP2 tagged with GFP at the C-terminus from a transgenic human PAC containing all known regulatory sequences. These transgenes were maintained on a wild-type pure FVB background. For experiments each transgenic line was crossed by Mecp2 null mice (Mecp2 tm1.1Bird) on a pure 129SvEv background and the resulting male F1 hybrid progeny (FVB;129SvEv) that lacked endogenous MeCP2 expression but expressed either transgene (Mecp2 -/y; MECP2-R270X TG or Mecp2-/y; MECP2-G273X TG) were used for ChIP-Seq analysis. Whole brain from either the R270X mice (Mecp2 -/y; MECP2-R270X TG) or the G273X mice (Mecp2 -/y; MECP2-G273X TG) was formaldehyde crosslinked and purified chromatin was immunoprecipitated with anti-GFP antibody (Abcam ab6556). 2 samples: R270X (Mecp2 -/y; MECP2-R270X TG) and G273X (Mecp2 -/y; MECP2-G273X TG) both on an F1 (FVB;129SvEv) hybrid background
2013-03-12 | E-GEOD-36536 | biostudies-arrayexpress
Project description:MeCP2 globally regulates gene expression in the brain. One example is Growth-differentiation factor 11 (Gdf11), which is down-regulated upon loss of MeCP2 and up-regulated upon gain of MeCP2. To assess if MeCP2 binds near the Gdf11 locus we performed CUT&RUN for MeCP2 in Mecp2-knockout or MECP2-transgenic hippocampus. To assess if a repressive histone modification (H3K27me3) was concordantly changed we profiled H3k27me3 in these same matched tissues.
2023-02-23 | GSE213752 | GEO
Project description:MECP2-R270X transgenic mice (TG) and MECP2-G273X TG mice were generated in the Zoghbi Lab. These mice express the respective truncated form of MeCP2 tagged with GFP at the C-terminus from a transgenic human PAC containing all known regulatory sequences. These transgenes were maintained on a wild-type pure FVB background. For experiments each transgenic line was crossed by Mecp2 null mice (Mecp2 tm1.1Bird) on a pure 129SvEv background and the resulting male F1 hybrid progeny (FVB;129SvEv) that lacked endogenous MeCP2 expression but expressed either transgene (Mecp2 -/y; MECP2-R270X TG or Mecp2-/y; MECP2-G273X TG) were used for ChIP-Seq analysis. Whole brain from either the R270X mice (Mecp2 -/y; MECP2-R270X TG) or the G273X mice (Mecp2 -/y; MECP2-G273X TG) was formaldehyde crosslinked and purified chromatin was immunoprecipitated with anti-GFP antibody (Abcam ab6556).
2013-03-12 | GSE36536 | GEO
Project description:We compared gene expression changes in the cerebellum of mice lacking MeCP2 (Mecp2-null) and mice overexpressing MeCP2 (MECP2-transgenic). A group of postnatal neurodevelopmental disorders collectively referred to as MeCP2 disorders are caused by aberrations in the gene encoding methyl-CpG-binding protein 2 (MECP2). Loss of MeCP2 function causes Rett syndrome (RTT), whereas increased copy number of the gene causes MECP2 duplication or triplication syndromes. MeCP2 acts as a transcriptional repressor, however the gene expression changes observed in the hypothalamus of MeCP2 disorder mouse models suggest that MeCP2 can also upregulate gene expression. To determine if this dual role of MeCP2 extends beyond the hypothalamus, we studied gene expression patterns in the cerebellum of Mecp2-null and MECP2-Tg mice, modeling RTT and MECP2 duplication syndrome, respectively. We found that abnormal MeCP2 dosage causes alterations in the expression of hundreds of genes in the cerebellum. The majority of genes were upregulated in MECP2-Tg mice and downregulated in Mecp2-null mice, consistent with a role for MeCP2 as a modulator that can both increase and decrease gene expression. Interestingly, many of the genes altered in the cerebellum, particularly those increased by the presence of MeCP2 and decreased in its absence, were similarly altered in the hypothalamus. Keywords: Comparison of cerebellar gene expression data between Mecp2-null mice and Mecp2-transgenic mice Total cerebellar RNA samples were collected from Mecp2-null male mice (n=5), MECP2-transgenic male mice (n=5), and their wild type male littermates at 6 weeks of age (n=5 for each group).
2010-04-10 | E-GEOD-15574 | biostudies-arrayexpress
Project description:We compared gene expression changes in the cerebellum of mice lacking MeCP2 (Mecp2-null) and mice overexpressing MeCP2 (MECP2-transgenic). A group of postnatal neurodevelopmental disorders collectively referred to as MeCP2 disorders are caused by aberrations in the gene encoding methyl-CpG-binding protein 2 (MECP2). Loss of MeCP2 function causes Rett syndrome (RTT), whereas increased copy number of the gene causes MECP2 duplication or triplication syndromes. MeCP2 acts as a transcriptional repressor, however the gene expression changes observed in the hypothalamus of MeCP2 disorder mouse models suggest that MeCP2 can also upregulate gene expression. To determine if this dual role of MeCP2 extends beyond the hypothalamus, we studied gene expression patterns in the cerebellum of Mecp2-null and MECP2-Tg mice, modeling RTT and MECP2 duplication syndrome, respectively. We found that abnormal MeCP2 dosage causes alterations in the expression of hundreds of genes in the cerebellum. The majority of genes were upregulated in MECP2-Tg mice and downregulated in Mecp2-null mice, consistent with a role for MeCP2 as a modulator that can both increase and decrease gene expression. Interestingly, many of the genes altered in the cerebellum, particularly those increased by the presence of MeCP2 and decreased in its absence, were similarly altered in the hypothalamus. Keywords: Comparison of cerebellar gene expression data between Mecp2-null mice and Mecp2-transgenic mice
2009-04-07 | GSE15574 | GEO
Project description:A group of postnatal neurodevelopmental disorders collectively referred to as MeCP2 disorders are caused by aberrations in the gene encoding methyl-CpG-binding protein 2 (MECP2). Loss of MeCP2 function causes Rett syndrome (RTT), whereas increased MeCP2 dosage causes MECP2 duplication or triplication syndromes. MeCP2 acts as a transcriptional repressor, however, the gene expression changes observed in the hypothalamus and cerebellum of MeCP2 disorder mouse models suggest that MeCP2 can also upregulate gene expression. In this study, we compared gene expression changes in the amygdalae of mice lacking MeCP2 (Mecp2-null) and mice overexpressing MeCP2 (MECP2-TG). We chose the amygdala because it is a neuroanatomical region implicated in the control of anxiety and social behavior, two prominent phenotypes in MECP2-TG mice, and hypothesized that transcriptional profiling of this particular brain region may reveal expression changes relevant to heightened anxiety-like behavior and abnormal social behavior. A total of 1,060 genes were altered in opposite directions in both MeCP2 mouse models compared with wild-type littermates, with ~60% up-regulated and ~40% down-regulated. Interestingly, we found a significant enrichment of anxiety- and/or social behavior-related genes among the differentially expressed genes. To determine whether these genes contribute to the anxiety and social behavior phenotypes in MECP2-TG mice, we performed genetic and pharmacologic studies and found that a reduction in Crh suppresses anxiety-like behavior, and a reduction in Oprm1 improves social approach behavior. These studies suggest that MeCP2 impacts molecular pathways involved in anxiety and social behavior, and provide insight into potential therapies for MeCP2 disorders. This study is published in Nature Genetics http://dx.doi.org/10.1038/ng.1066. Total amygdala RNA samples were collected from Mecp2-null male mice (n=4), MECP2-transgenic male mice (n=5), and their wild type male littermates at 6 weeks of age (n=4, n=5 for each group respectively).
2012-01-08 | E-GEOD-33457 | biostudies-arrayexpress
Project description:Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism. MECP2 encodes a methyl-DNA-binding protein that is proposed to function as a transcriptional repressor, but, despite numerous studies examining neuronal gene expression in MeCP2 mutants, no coherent model has emerged for how MeCP2 regulates transcription. Here we identify a genome-wide length-dependent increase in the expression of long genes in neurons lacking MeCP2. This gene misregulation occurs in human RTT brains and correlates with onset and severity of phenotypes in Mecp2 mutant mice, suggesting that the disruption of long gene expression contributes to RTT pathology. We present evidence that MeCP2 represses long genes by binding to brain-enriched, methylated CA dinucleotides within genes and show that loss of methylated CA in the brain recapitulates gene expression defects observed in MeCP2 mutants. We find that long genes encode proteins with neuronal functions, and overlap substantially with genes that have been implicated in autism and Fragile X syndrome. Reversing the overexpression of long genes in neurons lacking MeCP2 can improve some RTT-associated cellular deficits. These findings suggest that a function of MeCP2 in the mammalian brain is to temper the expression of genes in a length-dependent manner, and that mutations in MeCP2 and possibly other autism genes may cause neurological dysfunction by disrupting the expression of long genes in the brain.
2015-03-12 | GSE60074 | GEO