MeCP2-R270X and MeCP2-G273X ChIP-Seq
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Peng Yu
PROVIDER: E-GEOD-36536 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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: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.
2012-01-08 | GSE33457 | GEO
Project description:We compared gene expression changes in the hypothalamus of mice lacking MeCP2 (Mecp2-null) and mice overexpressing MeCP2 (MECP2-transgenic). Mutations in the gene encoding the transcriptional repressor methyl-CpG binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome. Loss of function as well as increased dosage of MECP2 gene cause a host of neuropsychiatric disorders. To explore the molecular mechanism(s) underlying these disorders, we examined gene expression patterns in the hypothalamus of mice that either lack or overexpress MeCP2. In both models, MeCP2 dysfunction induced changes in the expression levels of thousands of genes, but surprisingly the majority of genes (~85%) appeared to be activated by MeCP2. We selected six genes and confirmed that MeCP2 binds to their promoters. Furthermore, we showed that MeCP2 associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target. These studies suggest that MeCP2 regulates the expression of a wide range of genes in the hypothalamus and that it can function as both an activator and repressor of transcription. Total hypothalamic RNA samples were collected from Mecp2-null male mice (n=4), MECP2-transgenic male mice (n=4), and their wild type male littermates at 6 weeks of age (n=4 for each group).
2008-05-30 | E-GEOD-11150 | biostudies-arrayexpress
Project description:The study applied NGS to determine the cardiac transcriptomes of BBLN-transgenic mice with FVB/N background in comparison to those of non-transgenic FVB/N mice at an age of 8 months. The BBLN (Bublin coiled-coil protein) is the chromosome 9 open reading frame, C9orf16, with largely unknown function. To investigate the cardiac phenotype of increased cardiac BBLN transcript levels we generated BBLN-transgenic (Tg-BBLN) mice. Echocardiography documented that Tg-BBLN mice developed features of heart failure at an age of 8 months. To elucidate pathomechanisms of heart failure induced by BBLN, we performed NGS of the cardiac transcriptomes of eight-month-old, male, BBLN-transgenic mice with cardiac-specific expression of BBLN under control of the myocardium-specific, alpha-MHC promoter. The non-transgenic control group are age-matched, male, nontransgenic FVB/N mice. NGS data of this study document transcriptome changes underlying the heart failure phenotype induced by transgenic BBLN expression.
2023-09-18 | GSE241161 | GEO
Project description:Hearts of Myh6-MeCP2 transgenic mice and wildtype littermates were rapidly dissected and flash frozen. We used Affymetrix microarrays to assess gene expression changes induced by overexpression of MeCP2 under the control of a cardiomycyte specific promoter. Hearts were dissected 2-3 weeks after birth from transgenic Myh6-MeCP2 mice and littermates to study gene expression alterations.
2015-12-22 | E-GEOD-52797 | biostudies-arrayexpress
Project description:Cardiac-specific PPARalpha transgenic (Tg-PPARalpha) mice show mild cardiac hypertrophy and systolic dysfunction. The failing heart phenotypes observed in Tg-PPARalpha are exacerbated by crossing with cardiac-specific Sirt1 transgenic (Tg-Sirt1) mice, whereas Tg-Sirt1 mice themselves do not show any cardiac hypertrophy or systolic dysfunction. To investigate the mechanism leading to the failing heart phenotypes in TgPPARalpha/Tg-Sirt1 bigenic mice, microarray analyses were performed. The microarray analyses revealed that many ERR target genes were downregulated in Tg-PPARalpha and in Tg-Sirt1, and they were further downregulated in the Tg-PPARalpha/Tg-Sirt1 bigenic mice. Four groups of cardiac-specific transgenic mice were used for the study, i.e., control, PPARalpha, Sirt1 and PPARalpha/Sirt1. Hearts were dissected after 10-11 weeks of male FVB background transgenic mice. Total RNA was prepared from the hearts to conduct the microarray analyses.
2011-12-01 | E-GEOD-33101 | biostudies-arrayexpress
Project description:The postnatal neurodevelopmental disorder Rett syndrome (RTT) is caused by mutations in the gene encoding Methyl-CpG-binding Protein 2 (MeCP2). Despite decades of research, it remains unclear how MeCP2 actually regulates transcription or why RTT features appear only 6-18 months after birth. We examined MeCP2 binding to methylated cytosine in the CH context (mCH, where H = A, C, or T) in the adult mouse brain and found that MeCP2 binds these mCH sites, influencing nucleosome positioning and transcription. Strikingly, this pattern is unique to the mature nervous system, as it requires the increase in mCH after birth to reveal differences in MeCP2 binding to mCG, mCH, and non-methylated DNA elements. This study provides insight into the molecular mechanism governing MeCP2 targeting and how this targeting might contribute to the delayed onset of RTT symptoms. mRNA-Seq were conducted from 7-week-old hypothalamus from MeCP2 knockout mice and their age and genetic background matched wild types control mice. Additonal mRNA-Seq were conducted from 7-week-old hypothalamus from MeCP2 transgenic mice and their age and genetic background matched wild types control mice.
2015-04-15 | E-GEOD-66870 | biostudies-arrayexpress