Affinage

MECP2

Methyl-CpG-binding protein 2 · UniProt P51608

Length
486 aa
Mass
52.4 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MeCP2 is a methylated-DNA reader that translates DNA methylation patterns into transcriptional and chromatin states, principally in the nervous system (PMID:1408825, PMID:28450074). Its methyl-CpG binding domain (MBD) is necessary and sufficient to target methylated DNA, including heterochromatin, and reads both mCG and neuronal non-CG methylation (mCAC) as well as hydroxymethylated CA repeats via Arg133, with Rett-associated MBD mutations (T158M, R106W, P101S, R133C) destabilizing the domain and disrupting recognition (PMID:8524323, PMID:28450074, PMID:34324427); binding to non-CG mCAC sites is independently essential for brain function, since swapping MeCP2's MBD for the mCG-only MBD2 domain produces Rett-like phenotypes (PMID:33561390). The dominant repressive output of MeCP2 is to bridge methylated DNA to the NCoR/SMRT co-repressor complex through its NCoR interaction domain: a truncated protein retaining only the MBD and NID rescues Rett-like defects, and excessive NCoR recruitment via the TBL1X(R) subunit—not HDAC3 catalytic activity—drives MECP2 duplication toxicity (PMID:29019980, PMID:30463906). Mechanistically, MeCP2 represses transcriptional initiation by RNA Pol II at highly methylated long genes and at enhancers within megabase-scale topologically associating domains, without affecting elongation (PMID:31784358, PMID:31784360). MeCP2 also acts as a positive co-factor through direct interaction with RNA Pol II at CpG-island promoter-proximal regions in human neurons, conferring an activating role at a distinct gene set (PMID:38697112). Beyond direct transcription, MeCP2 organizes pericentric heterochromatin in concert with major-satellite RNA and constrains nucleosome occupancy on CA repeats (PMID:34324427, PMID:33296675), and influences intron retention by promoting recruitment of splicing factors near splice junctions (PMID:28480880). Its activity is gated post-translationally: phosphorylation drives nuclear-to-cytoplasmic redistribution that derepresses targets such as BDNF, importin α5 (KPNA1) controls its nuclear import, and PP2A/HIPK2 regulate its protein stability (PMID:28835516, PMID:29859319, PMID:30540948). Documented direct gene targets include Cdkl5, Kir4.1 (Kcnj10) in astrocytes, GFAP, and Sema5b/Robo2, establishing MeCP2 as a regulator across neuronal and glial cell types (PMID:20211261, PMID:29464197, PMID:26733807, PMID:24269336).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1992 Medium

    Established MeCP2 as a sequence-independent reader of methylated CpG DNA, defining its founding biochemical activity but leaving its physiological role open.

    Evidence Biochemical fractionation and in vitro transcription assays with purified MeCP2

    PMID:1408825

    Open questions at the time
    • In vitro transcription inhibition was non-specific, confounding the repression interpretation
    • No cellular or in vivo function established
    • No domain mapping of the methyl-binding activity
  2. 1996 High

    Mapped the methyl-binding function to the 85-aa MBD and showed methylation-dependent targeting to heterochromatin, defining the structural basis of MeCP2 recruitment.

    Evidence MeCP2-LacZ fusions with deletion analysis in wild-type and methylation-deficient cells

    PMID:8524323

    Open questions at the time
    • Did not identify downstream effectors recruited after targeting
    • Used a heterologous fusion reporter rather than endogenous protein
  3. 1998 High

    Connected methyl-DNA binding to active repression via the Sin3/HDAC corepressor axis, providing the first mechanistic model for how MeCP2 silences chromatin.

    Evidence Xenopus oocyte chromatin transcription assays with co-fractionation and TSA HDAC inhibition

    PMID:9620779

    Open questions at the time
    • Later work showed HDAC catalytic activity is not the toxicity mediator (#14)
    • Performed in reconstituted oocyte system, not neurons
  4. 2007 High

    Rigorously excluded DLX5/DLX6 as imprinted MeCP2 targets, correcting a candidate-target hypothesis and underscoring the need for direct binding evidence.

    Evidence Allele-specific expression in somatic cell hybrids and qRT-PCR in Mecp2-null vs WT mouse forebrain

    PMID:17701895

    Open questions at the time
    • A negative result; does not address genuine MeCP2 targets
    • Limited to imprinting context
  5. 2010 Medium

    Identified Cdkl5 as a methylation-dependent direct repression target, extending MeCP2 silencing to a specific neurodevelopmental gene.

    Evidence ChIP, siRNA knockdown, overexpression, and DNMT inhibition in rat brain

    PMID:20211261

    Open questions at the time
    • Single-lab study
    • Corepressor recruitment at this locus not dissected
  6. 2017 High

    Defined the minimal functional unit of MeCP2 as the MBD-NID module bridging methylated DNA to NCoR/SMRT, distilling the protein's essential role.

    Evidence Knock-in mice expressing truncated MeCP2 with behavioral rescue and AAV delivery

    PMID:29019980

    Open questions at the time
    • Does not exclude contributory roles for removed domains in chromatin/splicing functions
    • Rescue assessed by behavioral phenotype, not full molecular normalization
  7. 2017 High

    Showed MeCP2 reads neuronal non-CG mCA with high affinity and that Rett missense mutations destabilize the MBD, broadening the methylation marks it interprets.

    Evidence ITC and NMR biophysics with Rett-associated MBD mutants

    PMID:28450074

    Open questions at the time
    • Biophysical binding without genome-wide validation in this study
    • Single lab
  8. 2017 High

    Extended MeCP2 function to RNA processing, linking it to splicing-factor recruitment and intron retention.

    Evidence Mass-spectrometry interactome, RNA co-precipitation, knockdown, and Pol II occupancy

    PMID:28480880

    Open questions at the time
    • Mechanism connecting methyl-DNA binding to splicing-factor recruitment unclear
    • Generality across neuronal transcripts not established
  9. 2018 High

    Demonstrated that MECP2 duplication toxicity is driven by NCoR/SMRT recruitment via TBL1X(R), and decisively excluded HDAC3 catalysis as the effector.

    Evidence Knock-in mice with NCoR-interaction and HDAC3-deficient NCoR mutations, survival/phenotype analysis

    PMID:30463906

    Open questions at the time
    • Effector(s) downstream of NCoR recruitment beyond HDAC3 unresolved
    • Focused on overexpression toxicity rather than loss-of-function
  10. 2018 Medium

    Established post-translational control of MeCP2 abundance through PP2A/HIPK2, offering a therapeutic handle for duplication syndrome.

    Evidence RNAi kinase/phosphatase screen with in vivo PP2A inhibition in an MDS mouse model

    PMID:28835516

    Open questions at the time
    • Phosphosites and degradation pathway not fully defined
    • Single lab
  11. 2018 Medium

    Showed phosphorylation-dependent nuclear-to-cytoplasmic redistribution of MeCP2 derepresses BDNF, coupling signaling to target gene activation.

    Evidence Cocaine self-administration in vivo with subcellular localization and phospho/BDNF immunoblotting in human neurons and microglia

    PMID:29859319

    Open questions at the time
    • Specific phosphosite(s) and kinase not defined
    • Single lab
  12. 2018 Medium

    Identified importin α5 (KPNA1) as the nuclear import factor for MeCP2, defining how its nuclear localization is regulated.

    Evidence Importin α isoform-specific knockout mice with MeCP2 localization, gene expression, and behavioral readouts

    PMID:30540948

    Open questions at the time
    • NLS within MeCP2 not mapped
    • Single lab
  13. 2018 High

    Defined a cell-autonomous astrocytic role: MeCP2 directly regulates Kir4.1 to control potassium buffering, extending its function beyond neurons.

    Evidence ChIP, Mecp2-knockout astrocytes, electrophysiology, mRNA/protein quantification

    PMID:29464197

    Open questions at the time
    • Corepressor mechanism at this locus not dissected
    • Restricted to astrocyte K+ current phenotype
  14. 2019 High

    Resolved the transcriptional step MeCP2 acts on, showing NCoR-dependent suppression of Pol II initiation at long methylated genes with no effect on elongation.

    Evidence TT-seq and PRO-seq in mouse brain comparing Mecp2-null and NCoR-interaction-defective mutants

    PMID:31784358

    Open questions at the time
    • Does not address activating roles at other promoters (#22)
    • Mechanism of initiation suppression at molecular level not fully resolved
  15. 2019 High

    Linked MeCP2 repression to enhancers within methylation-rich TADs, showing genome topology shapes MeCP2-mediated regulation.

    Evidence ChIP-seq, ATAC-seq, and Hi-C in Mecp2-null mouse brain

    PMID:31784360

    Open questions at the time
    • Causal contribution of TAD structure vs methylation density not separated
    • Single rigorous study
  16. 2020 High

    Mapped non-CG mCAC binding as independently essential for brain function via a domain-swap, separating it from mCG-only recognition.

    Evidence MBD2-for-MBD domain-swap knockin mice with behavioral and expression phenotyping

    PMID:33561390

    Open questions at the time
    • Does not distinguish mCAC reading from secondary structural effects of the swapped domain
  17. 2020 Medium

    Implicated MeCP2 in pericentric heterochromatin organization through mutual targeting with major-satellite RNA and histone-mark deposition.

    Evidence RNA co-IP, ChIP for H3K9me3/H4K20me3, and domain/T158 mutant analysis in neurons and stem cells

    PMID:33296675

    Open questions at the time
    • Direct vs indirect RNA association not fully resolved
    • Single lab
  18. 2020 Medium

    Proposed that MeCP2 forms DNA-stimulated heterochromatin condensates disrupted by Rett mutations, framing a phase-separation model.

    Evidence Live-cell imaging, FRAP, and in vitro droplet assays with Rett mutants

    PMID:32698189

    Open questions at the time
    • Directly contradicted by more rigorous later work (#21)
    • In vitro condensate behavior may not reflect endogenous distribution
  19. 2021 High

    Provided structural and functional evidence that MeCP2 recognizes hydroxymethylated CA repeats via Arg133 and constrains nucleosome occupancy, defining a microsatellite-binding chromatin role.

    Evidence Crystal structure with hmCA DNA, nucleosome mapping, ChIP-seq, transcriptomics, and R133C analysis

    PMID:34324427

    Open questions at the time
    • Relationship of CA-repeat binding to NCoR-mediated repression not integrated
    • Functional contribution in vivo not assessed via genetics in this study
  20. 2022 High

    Identified the TCF20/PHF14 complex as a MeCP2 chromatin partner disrupted by Rett mutations, with in vivo genetic rescue of duplication phenotypes.

    Evidence BioID, reciprocal co-IP, ChIP, and Tcf20-reduction epistasis in MECP2 duplication mice

    PMID:35074918

    Open questions at the time
    • Molecular function of MeCP2-TCF20 at co-regulated genes not fully defined
    • Relationship to NCoR pathway unclear
  21. 2024 High

    Challenged the phase-separation model, showing MeCP2 nuclear distribution is governed by global DNA methylation rather than intrinsic condensate formation.

    Evidence FRAP, Mus spretus (lacking methylated satellite DNA), heterochromatin-disruption, and multi-species imaging

    PMID:38719804

    Open questions at the time
    • Does not exclude transient/local clustering at high-density methylation
    • Reconciliation with the prior condensate study left open
  22. 2024 High

    Revealed an activating arm of MeCP2 through direct RNA Pol II interaction at CpG-island promoters, establishing dual repressive and activating roles.

    Evidence CUT&Tag occupancy, co-IP/proteomics, and transcriptomics in human neurons with patient mutations

    PMID:38697112

    Open questions at the time
    • How activating vs repressing modes are selected at different loci unresolved
    • Direct Pol II contact surface not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MeCP2 partitions between NCoR-mediated repression, Pol II co-activation, splicing, and heterochromatin organization at a given locus, and the molecular logic that selects each output, remains unresolved.
  • No unified model integrating activating and repressing functions
  • Locus-selection rules for distinct effector recruitment unknown
  • Post-translational code controlling localization/stability incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3 GO:0003723 RNA binding 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 1
Partners
KPNA1MBD2NCOR1PHF14POLR2ATBL1XTCF20TRA2B
Complex memberships
NCoR/SMRT corepressor complexTCF20/PHF14 complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 MeCP2 was identified as a vertebrate protein that binds specifically to DNA containing methylated CpG pairs and is more tightly bound in the nucleus than MeCP1; purified MeCP2 inhibited transcription from both methylated and non-methylated DNA templates in vitro, likely due to non-specific DNA binding domains. Biochemical fractionation, in vitro transcription assay, chromatographic characterization Nucleic acids research Medium 1408825
1996 MeCP2 localizes to centromeric heterochromatin in mouse cells in a DNA methylation-dependent manner; the 85-amino-acid methyl-CpG binding domain (MBD) is necessary and sufficient for heterochromatic targeting, as shown by deletion analysis and expression in methylation-deficient mutant cells. MeCP2-LacZ fusion protein expression in wild-type and methylation-deficient mutant cells, deletion analysis, fluorescence microscopy Molecular and cellular biology High 8524323
1998 MeCP2 bound to methylated DNA co-fractionates with the Sin3 co-repressor and histone deacetylase (HDAC) to repress transcription in a chromatin context; inhibition of HDAC activity relieves MeCP2/methylated DNA-dependent transcriptional silencing and allows chromatin remodeling and transcriptional activation. Xenopus laevis oocyte transcription assay, chromatin assembly, co-fractionation, HDAC inhibitor (trichostatin A) treatment Nature genetics High 9620779
2009 In hepatic stellate cell myofibroblast transdifferentiation, MeCP2 is recruited to the 5' end of the PPARgamma locus, where it promotes H3K9 methylation and recruits the transcriptional repressor HP1alpha; MeCP2 also stimulates EZH2 expression leading to H3K27 methylation at the 3' exons of PPARgamma, forming a repressive chromatin structure. This epigenetic relay pathway involving MeCP2, EZH2, and miR132 controls liver fibrosis. Chromatin immunoprecipitation (ChIP), MeCP2-null mice in CCl4 fibrosis model, siRNA knockdown, qPCR, immunoblotting, miR132 transfection Gastroenterology High 19843474
2010 MeCP2 directly represses the Cdkl5 gene in a DNA methylation-dependent manner; increased MeCP2 levels repressed Cdkl5 in rat brain structures, while siRNA-mediated knockdown of Mecp2 or DNA methyltransferase inhibitors induced Cdkl5. ChIP demonstrated methylation-dependent MeCP2 binding to the Cdkl5 gene. siRNA knockdown, MeCP2 overexpression, DNA methyltransferase inhibitor treatment, ChIP, qPCR, in vivo cocaine model Neurobiology of disease Medium 20211261
2017 A radically truncated MeCP2 retaining only the methyl-CpG binding domain (MBD) and the NCoR/SMRT interaction domain (NID) — approximately half the native protein — rescues Rett syndrome-like neurological defects in mice, demonstrating that the primary functional requirement of MeCP2 is to physically bridge methylated DNA and the NCoR/SMRT co-repressor complex. Knock-in mice expressing truncated MeCP2 variants, behavioral phenotyping, AAV-mediated gene delivery to the brain, genetic reactivation Nature High 29019980
2017 MeCP2 depletion near splice junctions of retained introns reduces recruitment of splicing factors (including Tra2b), increases RNA polymerase II stalling, and thereby promotes intron retention. MeCP2 interactome analysis by mass spectrometry and RNA co-precipitation revealed that MeCP2 interacts with these splicing factors. Mass spectrometry (MeCP2 interactome), RNA co-precipitation, MeCP2 knockdown, intron retention analysis, RNA Pol II occupancy assay Nature communications High 28480880
2017 MeCP2 binds mCA (non-CG methylation, specifically methylated CpA) with high affinity in a strand-specific, orientation-dependent manner, while MBD2 does not show high affinity or methyl-specific binding to mCA; Rett-associated missense mutations (T158M, R106W, P101S) destabilize the MBD and disrupt recognition of both mCG and mCA equally. Isothermal titration calorimetry (ITC), NMR spectroscopy, Rett-associated missense mutants Journal of molecular biology High 28450074
2019 MeCP2 represses nascent RNA transcription of highly methylated long genes in the brain through its interaction with the NCoR co-repressor complex, specifically by reducing the rate of transcriptional initiation by RNA Pol II at transcription start sites, with no measurable effect on transcriptional elongation. TT-seq and PRO-seq (nascent RNA sequencing to measure initiation and elongation rates) in mouse brain, comparison in Mecp2-null and NCoR interaction-defective mutant mice Molecular cell High 31784358
2019 MeCP2 represses enhancers located within megabase-scale topologically associating domains (TADs) enriched for non-CG (mCH) and CG methylation; disruption of MeCP2 alters enhancer activity and leads to widespread changes in gene expression, providing a mechanism for how DNA topology shapes MeCP2-mediated gene regulation. Genome-wide MeCP2 ChIP-seq, ATAC-seq, Hi-C chromatin topology analysis, Mecp2-null mouse brain Molecular cell High 31784360
2020 MeCP2 is a dynamic component of heterochromatin condensates in cells and forms liquid-like condensates stimulated by DNA; multiple MeCP2 domains contribute to condensate formation; Rett syndrome-causing mutations disrupt condensate formation. MeCP2 condensates selectively incorporate heterochromatin cofactors rather than euchromatic transcriptional components. Live-cell imaging, FRAP, in vitro droplet/condensate assays, Rett mutant analysis, co-condensate partitioning assays Nature Medium 32698189
2021 MeCP2 binding to non-CG methylation (mCAC), not just mCG, is required for normal brain function; replacing MeCP2's MBD with the orthologous domain from MBD2 (which can only bind mCG) in knockin mice caused severe Rett-syndrome-like phenotypes, demonstrating that the interaction with neuronal mCAC sites is essential. Domain-swap knockin mouse model, behavioral phenotyping, gene expression analysis Molecular cell High 33561390
2021 MeCP2 is a microsatellite-binding protein that specifically recognizes hydroxymethylated CA repeats via Arg133 (a Rett-causing mutation hotspot); depletion of MeCP2 leads to nucleosome accumulation on CA repeats, altered chromatin organization of CA repeat-associated lamina domains, and genome-wide transcriptional dysregulation. Crystal structure of MeCP2 in complex with hmCA DNA reveals characteristic DNA shape recognition. Cryo-EM/crystal structure, MeCP2 depletion, nucleosome mapping, ChIP-seq, transcriptome analysis, R133C mutation analysis Science High 34324427
2022 MeCP2 interacts with a TCF20 complex (including PHF14) at the chromatin interface; Rett syndrome-causing MECP2 mutations disrupt the MeCP2-TCF20 interaction; MeCP2 and TCF20 co-regulate key neuronal genes; reducing Tcf20 partially rescues behavioral deficits in an MECP2 duplication mouse model. Proximity-dependent biotinylation (BioID), co-immunoprecipitation, ChIP, mouse genetic epistasis (Tcf20 reduction in MECP2 duplication mice), patient mutation analysis Proceedings of the National Academy of Sciences of the United States of America High 35074918
2018 A single amino acid substitution preventing MeCP2 from binding the TBL1X(R1) subunit of NCoR1/2 complexes abolishes overexpression toxicity in mice expressing ~4x wild-type MeCP2 levels, indicating that excessive NCoR/SMRT corepressor recruitment underlies MECP2 duplication toxicity. However, mutations drastically reducing HDAC3 catalytic activity in NCoR1/2 did not relieve toxicity, demonstrating that HDAC3 enzymatic activity is NOT the mediator of MeCP2 overexpression toxicity. Knock-in mouse models with NCoR-interaction mutant and HDAC3-activation-deficient NCoR1/2 mutations, survival and phenotypic analysis Genes & development High 30463906
2018 PP2A (protein phosphatase 2A) and HIPK2 (homeodomain-interacting protein kinase 2) were identified as stabilizers of MeCP2 in vivo; pharmacological inhibition of PP2A in vivo reduced MeCP2 protein levels in the nervous system and rescued motor abnormalities in a mouse model of MECP2 duplication syndrome. RNA interference screen against all human kinases and phosphatases, in vivo validation, pharmacological PP2A inhibition in MDS mouse model Science translational medicine Medium 28835516
2018 Cocaine induces phosphorylation of MeCP2 in microglia, causing its translocation from the nucleus to the cytosol, which frees the BDNF promoter from MeCP2-mediated repression and permits BDNF transcriptional activation. This was demonstrated in primary human neurons and microglia in vitro. Intravenous cocaine self-administration in vivo, immunofluorescence for MeCP2 subcellular localization, immunoblotting for phospho-MeCP2 and BDNF in human primary neurons and microglia Neurobiology of disease Medium 29859319
2018 Importin α5 (KPNA1) regulates MeCP2 nuclear import in hippocampal neurons; knockout of importin α5 (but not importin α3 or α4) reduces MeCP2 nuclear localization, leading to altered expression of MeCP2-regulated genes including sphingosine kinase 1 (Sphk1) and reduced anxiety behavior. Importin α knockout mouse lines, MeCP2 nuclear localization by immunofluorescence, behavioral testing, pharmacological Sphk1 blockade, re-expression rescue Cell reports Medium 30540948
2013 MeCP2 and MBD2 undergo direct homo- and hetero-interactions in vitro in the absence of DNA, and these interactions are confirmed by co-immunoprecipitation in mammalian cells and visualized in single cells by fluorescent two-hybrid assay. The region of MeCP2 comprising amino acids 163–309 mediates MeCP2-MBD2 association. In vitro interaction assay with recombinant purified proteins, co-immunoprecipitation, fluorescent two-hybrid assay, deletion analysis PloS one Medium 23335972
2018 MeCP2 is a direct molecular target of MeCP2 at the Kir4.1 (Kcnj10) locus in astrocytes; MeCP2-deficient mice show significantly reduced astrocytic Kir4.1 mRNA and protein, resulting in >50% deficiency in Ba2+-sensitive Kir4.1-mediated K+ currents and impaired extracellular potassium buffering. This loss is cell-autonomous. ChIP analysis showing MeCP2 binding to Kir4.1 locus, Mecp2-knockout mouse astrocytes, electrophysiology, mRNA/protein quantification eNeuro High 29464197
2020 MeCP2 and major satellite forward (MajSat-fw) RNA physically interact and are mutually required for their respective targeting to pericentric heterochromatin (PCH); MeCP2 promotes H3K9me3 and H4K20me3 deposition at PCH. The MeCP2-E2 isoform (MeCP2B) and the MBD and TRD domains, as well as residue T158, are required for correct higher-order PCH organization. Co-immunoprecipitation of MeCP2 with MajSat-fw RNA, ChIP for histone modifications, domain deletion analysis, T158 mutant analysis in neurons and stem cells Stem cell reports Medium 33296675
2024 MeCP2 does not have an intrinsic tendency to form phase-separated condensates; MeCP2 foci in mouse cells are absent in Mus spretus (which lacks methylated satellite DNA), persist when heterochromatin organization is disrupted (indicating MeCP2 localization is independent of heterochromatin), and fail to show hallmarks of liquid-liquid phase separation in live cells. In most mammalian species including humans, MeCP2 distribution is diffuse rather than punctate, indicating its nuclear distribution is primarily determined by global DNA methylation patterns. Live-cell imaging, FRAP, MeCP2 localization in Mus spretus and heterochromatin-disrupted cells, multi-species comparison Nature communications High 38719804
2024 MeCP2 directly interacts with RNA Polymerase II (RNA Pol II) and acts as a positive cofactor for RNA Pol II-dependent transcription at CpG island-containing promoter-proximal regions in human neurons; genes co-occupied by MeCP2 and RNA Pol II show reduced expression in neurons bearing MECP2 patient mutations, indicating MeCP2 has activating as well as repressing transcriptional roles. CUT&Tag for MeCP2 and RNA Pol II occupancy, proteomics/co-immunoprecipitation demonstrating direct MeCP2-RNA Pol II interaction, transcriptome analysis in human neurons with wild-type vs. mutant MECP2 Neuron High 38697112
2015 In zebrafish, Mecp2 deficiency results in downregulation of Sema5b and Robo2 in trigeminal sensory neurons, causing defects in peripheral innervation and sensory function; ChIP demonstrated MeCP2 binding to the promoters of Sema5b and Robo2, and cell-specific re-expression of Mecp2 rescued innervation defects in a cell-autonomous manner. mecp2-null zebrafish, morpholino knockdown, ChIP assay, cell-specific Mecp2 re-expression, sensory behavior assay Frontiers in cellular neuroscience Medium 26733807
2013 MeCP2 binds to the methylated GFAP promoter and suppresses GFAP expression in the developing brain; siRNA-mediated knockdown of MeCP2 in the female rat amygdala and hypothalamus specifically increased GFAP mRNA and protein, with this regulation being sex-specific (female but not male) and not affecting other astrocyte markers (S100β, vimentin). In vivo siRNA knockdown (MeCP2 siRNA infusion), qPCR and immunoblotting for GFAP and other astrocyte markers in neonatal rat brain Brain research Medium 24269336
2016 MeCP2 represses nuclear microRNA processing by directly interacting with the Drosha/DGCR8 complex, linking MeCP2 to post-transcriptional gene regulation. Co-immunoprecipitation of MeCP2 with Drosha/DGCR8, functional miRNA processing assays (as described in review citing primary experimental data) Neuroscience bulletin Low 25082535
2007 DLX5 and DLX6 are NOT imprinted in humans and are NOT direct targets of MeCP2 modulation; allele-specific expression was biallelic in somatic cell hybrids, human cell lines, and brain regardless of MeCP2 status; Dlx5/Dlx6 expression was highly variable with no consistent differences between Mecp2-null mutant and control mouse forebrains. In contrast, imprinted genes PEG3 and PEG10 maintain imprinting in MeCP2-deficient tissues. Somatic cell hybrid allele-specific expression analysis, real-time qRT-PCR in Mecp2-null vs. wild-type mice (n=7 null, n=8 WT), novel SNP genotyping American journal of human genetics High 17701895

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nature genetics 2130 9620779
1992 Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA. Nucleic acids research 443 1408825
2011 The role of MeCP2 in the brain. Annual review of cell and developmental biology 341 21721946
2009 MeCP2 controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis. Gastroenterology 335 19843474
1996 DNA methylation specifies chromosomal localization of MeCP2. Molecular and cellular biology 291 8524323
2014 Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome. Journal of medical genetics 255 24399845
2006 MeCP2 dysfunction in Rett syndrome and related disorders. Current opinion in genetics & development 198 16647848
2011 Adult neural function requires MeCP2. Science (New York, N.Y.) 197 21636743
2001 MeCP2 mutations in children with and without the phenotype of Rett syndrome. Neurology 188 11402105
2015 MECP2 disorders: from the clinic to mice and back. The Journal of clinical investigation 173 26237041
2020 MeCP2 links heterochromatin condensates and neurodevelopmental disease. Nature 162 32698189
2010 The role of MeCP2 in brain development and neurodevelopmental disorders. Current psychiatry reports 151 20425298
2019 The Molecular Basis of MeCP2 Function in the Brain. Journal of molecular biology 131 31629770
2014 Rett syndrome and MeCP2. Neuromolecular medicine 126 24615633
2017 Radically truncated MeCP2 rescues Rett syndrome-like neurological defects. Nature 124 29019980
2011 MECP2 Duplication Syndrome. Molecular syndromology 118 22679399
2007 MECP2 mutations in males. Journal of medical genetics 118 17351020
2001 Molecular genetics of Rett syndrome and clinical spectrum of MECP2 mutations. Current opinion in neurology 106 11262731
2009 Recent advances in MeCP2 structure and function. Biochemistry and cell biology = Biochimie et biologie cellulaire 101 19234536
2021 MeCP2: The Genetic Driver of Rett Syndrome Epigenetics. Frontiers in genetics 100 33552148
2011 Experimental models of Rett syndrome based on Mecp2 dysfunction. Experimental biology and medicine (Maywood, N.J.) 99 21239731
2000 Rett syndrome: a surprising result of mutation in MECP2. Human molecular genetics 99 11005791
2019 MeCP2 Represses the Rate of Transcriptional Initiation of Highly Methylated Long Genes. Molecular cell 92 31784358
2003 Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis. Molecular and cellular neurosciences 92 12727440
2017 Intron retention is regulated by altered MeCP2-mediated splicing factor recruitment. Nature communications 87 28480880
2002 Associations between MeCP2 mutations, X-chromosome inactivation, and phenotype. Mental retardation and developmental disabilities research reviews 86 12112735
2017 Site-directed RNA repair of endogenous Mecp2 RNA in neurons. Proceedings of the National Academy of Sciences of the United States of America 85 29078406
2012 The relationship of Rett syndrome and MECP2 disorders to autism. Dialogues in clinical neuroscience 84 23226951
2010 CDKL5 is a brain MeCP2 target gene regulated by DNA methylation. Neurobiology of disease 84 20211261
2014 MeCP2: the long trip from a chromatin protein to neurological disorders. Trends in molecular medicine 83 24766768
2008 MECP2 promoter methylation and X chromosome inactivation in autism. Autism research : official journal of the International Society for Autism Research 79 19132145
2016 MECP2, a multi-talented modulator of chromatin architecture. Briefings in functional genomics 76 27296483
2011 MeCP2: structure and function. Biochemistry and cell biology = Biochimie et biologie cellulaire 74 21326358
2009 Evolving role of MeCP2 in Rett syndrome and autism. Epigenomics 73 20473347
2023 Multiplex epigenome editing of MECP2 to rescue Rett syndrome neurons. Science translational medicine 70 36652535
2005 MeCP2 dysfunction in humans and mice. Journal of child neurology 68 16225828
2011 MeCP2 and Rett syndrome: reversibility and potential avenues for therapy. The Biochemical journal 67 21916843
2008 Rett syndrome and the impact of MeCP2 associated transcriptional mechanisms on neurotransmission. Biological psychiatry 63 19058783
2017 The Crucial Role of DNA Methylation and MeCP2 in Neuronal Function. Genes 62 28505093
2019 MeCP2 Represses Enhancers through Chromosome Topology-Associated DNA Methylation. Molecular cell 61 31784360
2016 Rett syndrome - biological pathways leading from MECP2 to disorder phenotypes. Orphanet journal of rare diseases 57 27884167
2015 Exploring the possible link between MeCP2 and oxidative stress in Rett syndrome. Free radical biology & medicine 57 25960047
2022 Rett Syndrome and MECP2 Duplication Syndrome: Disorders of MeCP2 Dosage. Neuropsychiatric disease and treatment 55 36471747
2016 Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus. Cell research 55 27103432
2013 DNA methylation and MeCP2 regulation of PTCH1 expression during rats hepatic fibrosis. Cellular signalling 55 23333245
2017 MeCP2 mutations: progress towards understanding and treating Rett syndrome. Genome medicine 54 28212680
2010 The role of MeCP2 in CNS development and function. Hormones and behavior 53 20515694
2018 Cocaine-mediated activation of microglia and microglial MeCP2 and BDNF production. Neurobiology of disease 47 29859319
2018 MECP2 Mutation Interrupts Nucleolin-mTOR-P70S6K Signaling in Rett Syndrome Patients. Frontiers in genetics 47 30619462
2017 MiR-218 targets MeCP2 and inhibits heroin seeking behavior. Scientific reports 47 28074855
2012 MECP2 duplication syndrome in both genders. Brain & development 46 22877836
2021 Neuronal non-CG methylation is an essential target for MeCP2 function. Molecular cell 45 33561390
2007 DLX5 and DLX6 expression is biallelic and not modulated by MeCP2 deficiency. American journal of human genetics 44 17701895
2014 MeCP2: multifaceted roles in gene regulation and neural development. Neuroscience bulletin 43 25082535
2005 Large genomic rearrangements in MECP2. Human mutation 43 15712379
2002 The phenotypic consequences of MECP2 mutations extend beyond Rett syndrome. Mental retardation and developmental disabilities research reviews 43 12112734
2006 Mechanisms of disease: neurogenetics of MeCP2 deficiency. Nature clinical practice. Neurology 42 16932552
2024 MECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons. Neuron 41 38697112
2021 MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion. Science (New York, N.Y.) 41 34324427
2008 MECP2 genomic structure and function: insights from ENCODE. Nucleic acids research 41 18820302
2022 Disruption of MeCP2-TCF20 complex underlies distinct neurodevelopmental disorders. Proceedings of the National Academy of Sciences of the United States of America 37 35074918
2020 Accelerated Hyper-Maturation of Parvalbumin Circuits in the Absence of MeCP2. Cerebral cortex (New York, N.Y. : 1991) 37 31038696
2017 Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation. Disease models & mechanisms 37 28993314
2016 Reciprocal regulation of autism-related genes MeCP2 and PTEN via microRNAs. Scientific reports 37 26843422
2023 MeCP2 Is an Epigenetic Factor That Links DNA Methylation with Brain Metabolism. International journal of molecular sciences 36 36835623
2020 MeCP2 and Chromatin Compartmentalization. Cells 36 32260176
2022 Regulation of BDNF transcription by Nrf2 and MeCP2 ameliorates MPTP-induced neurotoxicity. Cell death discovery 35 35595779
2017 Structural Basis of MeCP2 Distribution on Non-CpG Methylated and Hydroxymethylated DNA. Journal of molecular biology 35 28450074
2017 MeCP2 Regulates PTCH1 Expression Through DNA Methylation in Rheumatoid Arthritis. Inflammation 35 28573530
2010 MeCP2 and drug addiction. Nature neuroscience 35 20740030
2013 Direct homo- and hetero-interactions of MeCP2 and MBD2. PloS one 34 23335972
2007 MeCP2 in Rett syndrome: transcriptional repressor or chromatin architectural protein? Current opinion in genetics & development 34 17317146
2021 The Molecular Functions of MeCP2 in Rett Syndrome Pathology. Frontiers in genetics 33 33968128
2021 MECP2-Related Disorders in Males. International journal of molecular sciences 33 34502518
2015 Role of mecp2 in experience-dependent epigenetic programming. Genes 33 25756305
2013 MeCP2 regulates GFAP expression within the developing brain. Brain research 33 24269336
2021 MECP2 and the biology of MECP2 duplication syndrome. Journal of neurochemistry 32 33638179
2005 MeCP2 in neurons: closing in on the causes of Rett syndrome. Human molecular genetics 32 15809268
2019 MeCP2: an epigenetic regulator of critical periods. Current opinion in neurobiology 31 31163286
2018 MeCP2 Deficiency Leads to Loss of Glial Kir4.1. eNeuro 31 29464197
2002 Identification of a family with nonspecific mental retardation (MRX79) with the A140V mutation in the MECP2 gene: is there a need for routine screening? Human mutation 31 12325019
2017 An RNA interference screen identifies druggable regulators of MeCP2 stability. Science translational medicine 30 28835516
2018 Importin α5 Regulates Anxiety through MeCP2 and Sphingosine Kinase 1. Cell reports 28 30540948
2005 Dissecting MECP2 function in the central nervous system. Journal of child neurology 28 16225831
2012 Altered microtubule dynamics in Mecp2-deficient astrocytes. Journal of neuroscience research 27 22252744
2001 Cytogenetic and molecular-cytogenetic studies of Rett syndrome (RTT): a retrospective analysis of a Russian cohort of RTT patients (the investigation of 57 girls and three boys). Brain & development 27 11738872
2018 Toxicity of overexpressed MeCP2 is independent of HDAC3 activity. Genes & development 26 30463906
2015 Circadian cycle-dependent MeCP2 and brain chromatin changes. PloS one 26 25875630
2022 Prime editing optimized RTT permits the correction of the c.8713C>T mutation in DMD gene. Molecular therapy. Nucleic acids 25 36320324
2014 Mild expression differences of MECP2 influencing aggressive social behavior. EMBO molecular medicine 25 24648499
2013 MeCP2 regulates ethanol sensitivity and intake. Addiction biology 25 23448145
2022 Selective Xi reactivation and alternative methods to restore MECP2 function in Rett syndrome. Trends in genetics : TIG 24 35248405
2003 MECP2 and beyond: phenotype-genotype correlations in Rett syndrome. Journal of child neurology 24 14649547
2022 MECP2-related pathways are dysregulated in a cortical organoid model of myotonic dystrophy. Science translational medicine 22 35767654
2024 MeCP2 binds to methylated DNA independently of phase separation and heterochromatin organisation. Nature communications 20 38719804
2023 The Epigenetic Reader Methyl-CpG-Binding Protein 2 (MeCP2) Is an Emerging Oncogene in Cancer Biology. Cancers 20 37345019
2020 MeCP2 and Major Satellite Forward RNA Cooperate for Pericentric Heterochromatin Organization. Stem cell reports 20 33296675
2015 Methyl-CpG Binding Protein 2 (Mecp2) Regulates Sensory Function Through Sema5b and Robo2. Frontiers in cellular neuroscience 20 26733807
2009 Variable phenotypic expression of a MECP2 mutation in a family. Journal of neurodevelopmental disorders 20 20151026
2020 MeCP2 in cholinergic interneurons of nucleus accumbens regulates fear learning. eLife 19 32420873

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