Study of MeCP2 binding and accessibity of chromatin in absence and presence of MeCP2 using ATAC-seq
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE125658 | GEO | 2019/06/27
REPOSITORIES: GEO
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Project description:Study of MeCP2 binding and accessibity of chromatin in absence and presence of MeCP2 using ATAC-seq
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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:Rett syndrome is a human intellectual disability disorder that is associated with mutations in the X-linked MECP2 gene. Theepigenetic reader MeCP2 binds to methylated cytosines on the DNA and regulates chromatin organization. We have shownpreviously that MECP2 Rett syndrome missense mutations are impaired in chromatin binding and heterochromatinreorganization. Here, we performed a proteomics analysis of post-translational modifications of MeCP2 isolated from adult mousebrain. We show that MeCP2 carries various post-translational modifications, among them phosphorylation on S80 and S421, whichlead to minor changes in either heterochromatin binding kinetics or clustering. We found that MeCP2 is (di)methylated on severalarginines and that this modification alters heterochromatin organization. Interestingly, we identified the Rett syndrome mutationsite R106 as a dimethylation site. In addition, co-expression of protein arginine methyltransferases 1 and 6 lead to a decrease ofheterochromatin clustering. Altogether, we identified and validated novel modifications of MeCP2 in the brain and show that thesecan modulate its ability to bind as well as reorganize heterochromatin, which may play a role in the pathology of Rett syndrome.
2022-10-15 | PXD033696 | Pride
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:Although methyl CpG binding domain protein-2 (MeCP2) is commonly understood to function as a silencing factor at methylated DNA sequences, recent studies also show that MeCP2 can bind unmethylated sequences and coordinate gene activation. MeCP2 displays broad binding patterns throughout the genome, with high expression levels similar to histone H1 in neurons. Despite its significant presence in the brain, only subtle gene expression changes occur in the absence of MeCP2. This may reflect a more complex regulatory mechanism of MeCP2 to complement chromatin binding. Using an RNA immunoprecipitation of native chromatin technique, we identify MeCP2 interacting microRNAs in mouse primary cortical neurons. In addition, comparison with mRNA sequencing data from Mecp2-null mice suggests that differentially expressed genes may indeed be targeted by MeCP2-interacting microRNAs. These findings highlight the MeCP2 interaction with microRNAs that may modulate its binding with chromatin and regulate gene expression.
2018-05-22 | GSE107085 | GEO
Project description:MeCP2 ChIP-seq was performed to study localisation of MeCP2 in the genome and to confirm binding to mCG.
2019-06-27 | GSE125659 | GEO
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 plays a multifaceted role in gene expression regulation and chromatin organization. Interaction between MeCP2 and methylated DNA to regulate gene expression is well established. However, the widespread MeCP2 distribution suggests its additional interactions with chromatin. Here we show, by both biochemical and ChIP-seq analyses, that MeCP2 directly binds to nucleosome subunit proteins and is recruited to distinct chromatin regions where H3K27me3 is enriched. We further observed that the impact of MeCP2 on transcriptional changes is correlated with histone post-translational modification patterns. Our findings indicate that MeCP2 can be recruited to genomic loci via indirect binding and that interaction between MeCP2 and histone proteins plays a significant role in gene expression regulation.
2018-11-10 | GSE122364 | GEO
Project description:MeCP2 plays a multifaceted role in gene expression regulation and chromatin organization. Interaction between MeCP2 and methylated DNA to regulate gene expression is well established. However, the widespread MeCP2 distribution suggests its additional interactions with chromatin. Here we show, by both biochemical and ChIP-seq analyses, that MeCP2 directly binds to nucleosome subunit proteins and is recruited to distinct chromatin regions where H3K27me3 is enriched. We further observed that the impact of MeCP2 on transcriptional changes is correlated with histone post-translational modification patterns. Our findings indicate that MeCP2 can be recruited to genomic loci via indirect binding and that interaction between MeCP2 and histone proteins plays a significant role in gene expression regulation.
2019-08-22 | GSE136119 | GEO
Project description:MeCP2 plays a multifaceted role in gene expression regulation and chromatin organization. Interaction between MeCP2 and methylated DNA to regulate gene expression is well established. However, the widespread MeCP2 distribution suggests its additional interactions with chromatin. Here we show, by both biochemical and ChIP-seq analyses, that MeCP2 directly binds to nucleosome subunit proteins and is recruited to distinct chromatin regions where H3K27me3 is enriched. We further observed that the impact of MeCP2 on transcriptional changes is correlated with histone post-translational modification patterns. Our findings indicate that MeCP2 can be recruited to genomic loci via indirect binding and that interaction between MeCP2 and histone proteins plays a significant role in gene expression regulation.
2019-08-22 | GSE136118 | GEO