ライフサイエンスコーパス: MeCP2

1 ription factor Methyl CpG Binding Protein 2 (MECP2).

2 onal regulator methyl-CpG-binding protein 2 (MeCP2).

3 onal regulator methyl-CpG-binding protein 2 (MeCP2).

4 actors such as methyl-CpG-binding protein 2 (MeCP2).

5 y mutations in Methyl-CpG-binding protein 2 (MECP2).

6 ions in the methyl-CpG binding protein gene (MECP2).

7 ns in the methyl-CpG-binding protein 2 gene (MECP2).

8 cupancy of methylcytosine binding protein 2 (MeCP2).

9 sidues of TBLR1 and TBL1 disrupts binding to MeCP2.

10 d was recruited to active gene promoters via MeCP2.

11 CC2) is a critical downstream gene target of MeCP2.

12 l with an X chromosome duplication including MECP2.

13 be the primary driver of gene repression by MeCP2.

14 orrelation with the functional impairment of MeCP2.

15 is repressed by methylation and may include MeCP2.

16 ed the heterochromatin clustering ability of MeCP2.

17 aches must restore close to normal levels of MECP2.

18 eversed the impaired exploratory behavior in Mecp2(308/y) male mice.

19 By linking for the first time neuronal MeCP2, a key player in brain development, to immune acti

20 cting protein kinase2 (HIPK2) phosphorylates MeCP2, a known transcriptional repressor.

21 tes within the brain results in depletion of MeCP2 across genes that normally contain a high density

22 near-normal; and those expressing a minimal MeCP2 additionally lacking a central domain survive for

23 rities and differences caused by the loss of MeCP2 among divergent rodent species which may have impo

24 tions as an epigenetic switch redistributing MeCP2 among mCG and mCA loci.

25 gene encoding methyl-CpG binding protein 2 (MECP2), an epigenetic regulator of mRNA transcription.

26 A is bound by the methyl-DNA-binding protein MECP2 and functions in a rheostat-like manner to fine-tu

27 However, it is not known if MeCP2 and HIPK2 are involved in processing of miRNAs imp

28 Xq28 chromosomal deletion encompassing both MECP2 and IRAK1 Like many boys with MECP2 null mutations

29 MeCP2 and its partners, splicing factor Y-box binding pr

30 ized with the methylated DNA binding protein MeCP2 and with the active chromatin histone modification

31 2 disorders (constitutive Mecp2 null, mosaic Mecp2(+/-), and MECP2 duplication): abnormally elevated

32 ects using the methyl-CpG-binding protein 2 (MeCP2) and beta-actin promoters to drive low versus high

33 These findings position MeCP2 as a novel component in metabolic homeostasis.

34 Since the identification of MECP2 as the causative gene in the majority of Rett Synd

35 ghting new molecular players ANT3, DFS70 and MeCp2 associated to glaucoma.

36 f promoter IV complex via phosphorylation of MeCP2 at Ser421 by Protein Kinase A (PKA).

37 demonstrate a novel role for the SIAH1/HIPK2/MeCP2 axis in suppressing miR-25 processing and thereby

38 These results demonstrate that MeCP2 behaves like a repressor even in the absence of me

39 Additionally, MeCP2 behaves similarly to histone H1 and HMGD1 in creat

40 Integrating MeCP2 binding and DNA methylation in a probabilistic gra

41 Finally, MeCP2 binding downstream of promoters correlates with in

42 s, oxidation of 5mCA to 5hmCA does not alter MeCP2 binding or expression of adjacent genes.

43 rimetry and NMR spectroscopy to characterize MeCP2 binding to methylated and hydroxymethylated mCG an

44 We found that the T158M mutation impaired MECP2 binding to methylated DNA and destabilized MeCP2 p

45 matic foci, reflecting restoration of normal MeCP2 binding to methylated DNA.

46 in "functional" demethylation and diminished MeCP2 binding, thus facilitating transcription.

47 ed with intellectual disability also prevent MeCP2 binding.

48 These analyses reveal that MeCP2 binds mCA with high affinity in a strand-specific

49 increased levels of the epigenetic regulator MeCP2, bringing to disruption of dendritic spine morphol

50 ations in methyl-CpG binding protein 2 gene (Mecp2), but fundamental aspects of its physiological mec

51 thin the body of genes normally repressed by MeCP2, but also enriched within extended megabase-scale

52 ping techniques have revealed, however, that MeCP2 can bind asymmetrically methylated and hydroxymeth

53 Thus, mutations in MECP2 can have secondary effects on DNA methylation and

54 Mutations in MECP2 cause Rett syndrome (RTT), an X-linked neurologica

55 gene encoding methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome (RTT), a neurological disorde

56 tly, we find that liver targeted deletion of Mecp2 causes fatty liver disease and dyslipidemia simila

57 Furthermore, MeCP2 co-localizes with nucleosomes.

58 1 (DFS70) and methyl-CpG-binding protein 2 (MeCp2) could be documented by MS.

59 fluoxetine treatment could disassociate the MeCP2-CREB-Bdnf promoter IV complex via phosphorylation

60 MeCP2 deficiency in glutamatergic neurons leads to early

61 Chronic block of TrkB receptors mimics the MeCP2 deficiency in wildtype glutamatergic neurons, whil

62 nd neuronal differentiation brought about by MeCP2 deficiency using both monolayer and three-dimensio

63 We describe here a boy with X-linked MECP2 deficiency-related syndrome due to a large de novo

64 re-expression of BDNF quantitatively rescues MeCP2 deficiency.

65 administration of a GABA reuptake blocker in MECP2 deficient mice markedly reduced the occurrence of

66 We used a MECP2 deficient mouse model of RTT as a strategy to obta

67 e of rescuing growth deficits in neighboring MeCP2 deficient neurons in vitro and in vivo.

68 product, was found to restore MT dynamics in Mecp2-deficient astrocytes and in MECP2 p.Arg294* iPSC-d

69 T)-dependent vesicle transport is altered in Mecp2-deficient astrocytes from newborn Mecp2-deficient

70 We show that in Mecp2-deficient male mice, whisker-evoked activity is ro

71 e neurological symptoms when introduced into MeCP2-deficient mice by genetic activation or virus-medi

72 d in Mecp2-deficient astrocytes from newborn Mecp2-deficient mice compared with control wild-type lit

73 on of these mice with wild type and globally MeCP2-deficient mice showed that the majority of RTT-ass

74 Additionally, treatment of Mecp2-deficient mice with VU0462807 improves motor perfo

75 onal (cerebral organoid) patient-derived and MeCP2-deficient neuronal culture models.

76 We show that Mecp2-deficient neurons also lack homeostatic synaptic p

77 e expression studies comparing wild-type and MeCP2-deficient neurons have failed to identify gene exp

78 Interestingly, overexpression of KCC2 in MeCP2-deficient neurons rescued GABA functional deficits

79 restored homeostatic synaptic plasticity in Mecp2-deficient neurons, providing novel targets of inte

80 ters correlates with increased expression in Mecp2-deficient neurons.

81 In the present study, we show that Mecp2 deletion had no effect on brain and reduced serum

82 Mecp2 deletion in mice results in an imbalance of excita

83 effects on motor deficits and survival when Mecp2 deletion was expressed on a background strain (C57

84 the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) an

85 circuit dysfunction in three mouse models of MECP2 disorders (constitutive Mecp2 null, mosaic Mecp2(+

86 rder caused by loss-of-function mutations in MECP2, display impaired excitatory neurotransmission, th

87 e to adenosine (G > A) mutation in the mouse MeCP2 DNA binding domain.

88 tion sizes, to study the impact of increased MeCP2 dosage in human neurons.

89 nt stem cells (iPSCs) from patients with the MECP2 duplication syndrome (MECP2dup), carrying differen

90 odel recapitulates early stages of the human MECP2 duplication syndrome and represents a promising ce

91 stitutive Mecp2 null, mosaic Mecp2(+/-), and MECP2 duplication): abnormally elevated synchrony in the

92 gene, and in Rett-related disorders, such as MECP2 duplication.

93 ific effect of methyl-CpG-binding protein-2 (MeCP2) dysfunction on iPSC-derived neuronal migration an

94 , we generated conditional mouse models with Mecp2 either removed from or expressed solely in glutama

95 Restoring Mecp2 expression exclusively in the somatosensory neuron

96 Because restoration of MeCP2 expression in a mouse model reverses neurologic de

97 Surprisingly, we found that MeCP2 expression in the HoxA4 domain alone is critical f

98 In turn, viral-mediated knockdown of MeCP2 expression in the NAc core reduces methamphetamine

99 Here we show that genetically restoring Mecp2 expression only in GABAergic neurons of male Mecp2

100 Genetic restoration of MeCP2 expression reverses RTT-like phenotypes in mice, h

101 Furthermore, loss or gain of Mecp2 expression specifically in microglia (Cx3cr1(CreER

102 However, MeCP2 expression within components of the breathing circ

103 ion specifically in microglia (Cx3cr1(CreER);Mecp2(fl/y)or Cx3cr1(Cr)(eER); Mecp2(LSL/y)) had little

104 essential role of striatal Hdac1, Hdac2 and MeCP2 for suppression of repetitive behaviors.

105 Loss of MeCP2 from a specific interneuron subtype contributes cr

106 argely reproduced in mice simply by removing MeCP2 from inhibitory GABAergic neurons.

107 RTT missense MECP2(R306C) mutation prevents MeCP2 from interacting with the NCoR/histone deacetylase

108 Here we show that MeCP2 function plays distinct roles in specific brainste

109 characterized cardiac rhythm in mice lacking Mecp2 function.

110 gest therapeutic opportunities to manipulate MeCP2 function.

111 the methyl-CpG-binding domain (MBD) family, MeCP2 functions through the recognition of symmetrical 5

112 We report that mice harboring mutations in Mecp2, Gabrb3, Shank3, and Fmr1 genes associated with AS

113 Mutations in the MECP2 gene cause Rett syndrome (RTT).

114 Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett sy

115 Heterozygous mutations in the X-linked MECP2 gene cause the neurological disorder Rett syndrome

116 A distinct disorder results from MECP2 gene duplication, suggesting that therapeutic appr

117 Manipulations of the Mecp2 gene in mice provide useful models to probe into v

118 dominant disorder caused by mutations in the MECP2 gene, and in Rett-related disorders, such as MECP2

119 disorder caused by mutation of the X-linked MECP2 gene, which results in the progressive disruption

120 der resulting from mutations in the X-linked MECP2 gene.

121 opmental disorder caused by mutations in the MECP2 gene.

122 d by loss-of-function mutations in the human MECP2 gene.

123 tations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic

124 tations in the methyl-CpG-binding protein 2 (MeCP2) gene.

125 utation in the Methyl-CpG-binding protein-2 (MeCP2) gene.

126 ransgene expression after intravenous scAAV9/MeCP2-GFP injection was primarily detected in NeuN(+) ne

127 Accordingly, MeCP2 has been cast as a multi-functional hub that integ

128 Functionally, MeCP2 has been implicated in several cellular processes

129 and other posttranslational modifications of MeCP2 have been described recently to modulate its funct

130 Although postnatal functions of MeCP2 have been thoroughly investigated, its role in pre

131 onal modulator Methyl-CpG-Binding Protein 2 (MeCP2) have advanced our understanding of Rett syndrome

132 eiving scAAV9/beta-actin-hCLN3 versus scAAV9/MeCP2-hCLN3 after a single systemic injection.

133 However, only scAAV9/MeCP2-hCLN3 corrected motor deficits and attenuated glia

134 e systemic (intravenous) injection of scAAV9/MeCP2-hCLN3 or scAAV9/beta-actin-hCLN3, with green fluor

135 eiving scAAV9/beta-actin-hCLN3 versus scAAV9/MeCP2-hCLN3.

136 oral assessments have been conducted in male Mecp2 hemizygous null mice as offspring of heterozygous

137 In response to learned maternal experience, Mecp2(het) females exhibited transient changes to cortic

138 y cortical plasticity are impaired in female Mecp2(het) mice, a model of Rett syndrome.

139 Averting these changes in Mecp2(het) through genetic or pharmacological manipulati

140 y in auditory cortex that is dysregulated in Mecp2(het).

141 from early postnatal to adult ages in female Mecp2 heterozygotes of the conventional Bird line (Mecp2

142 ys was enhanced in amplitude and duration in Mecp2 heterozygous female mice.

143 macological activation of CREB in the female Mecp2 heterozygous mice rescued several behavioral defec

144 In this study, we found that: (i) Mecp2 heterozygous mice showed deficiency of GABA periso

145 Furthermore, histone H1 and MeCP2 hinder model transcription factor Gal4 from bindin

146 ng the molecular consequences of the loss of MeCP2 in both mouse and rat may result in higher predict

147 nvestigate genes that function downstream of MeCP2 in cerebral cortex circuitry, and identify upregul

148 ssed gene bodies while retaining the role of MeCP2 in chromatin organization.

149 Here we explore the mechanism of mCA and MeCP2 in fine tuning the expression of long genes.

150 eostatic mechanisms, we examined the role of MeCP2 in homeostatic synaptic plasticity (HSP) at excita

151 m initiation and progression upon removal of MeCP2 in male mice transitions from 3 to 4 months to onl

152 Deletion of Mecp2 in mice results in an imbalance of synaptic excita

153 hod for cell-type-specific biotin tagging of MeCP2 in mice.

154 we show poly(ADP-ribosyl)ation of endogenous MeCP2 in mouse brain tissue.

155 Recent work suggests that one function of MeCP2 in neurons is to temper the expression of the long

156 Thus, loss of MeCP2 in the brain alters both excitation and inhibition

157 ic, and 2) a new cell-type specific role for Mecp2 in the development of NMDAR subunit composition.

158 S, methamphetamine SA, and the expression of MeCP2 in the NAc may represent novel mechanisms that can

159 increased the chromatin binding affinity of MeCP2 in vivo.

160 etic regulator methyl CpG-binding protein 2 (MeCP2) in key brain reward regions, particularly in the

161 e encoding the transcriptional repressor and MeCP2 interactor switch-insensitive 3 family member A (S

162 ated by methylcytosine binding proteins like MeCP2 into chromatin topology and structure and gene act

163 Our study reveals that MeCP2 is differentially required in select respiratory c

164 lar mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range

165 f the NMDAR subunit, GluN2A, in mice lacking Mecp2 is sufficient to prevent RTT phenotypes, including

166 othesis that the single dominant function of MeCP2 is to physically connect DNA with the NCoR/SMRT co

167 Furthermore, NAc core MeCP2 knockdown reduces methamphetamine, but not sacchar

168 nd neuronal migration in a similar manner to Mecp2 knockdown.

169 Hippocampal neurons from Mecp2 knockout (KO) mice do not show the characteristic

170 n-aggregated structures in the cerebellum of Mecp2 knockout mouse model (Mecp2 (-/y) ) during transit

171 In Mecp2 KO mice, we found that mGluR5 NAM treatment signif

172 fected in slices from younger presymptomatic Mecp2 KO mice.

173 This deficit in HSP is bidirectional because Mecp2 KO neurons also failed to scale down mEPSC amplitu

174 of AMPA-type of glutamate receptors in HSP, Mecp2 KO neurons have lower levels of early endosome ant

175 ntification of a molecular deficit in HSP in Mecp2 KO neurons provides potentially novel targets of i

176 In addition, expression of EEA1 in Mecp2 KO neurons reduced mEPSC amplitudes to wild-type l

177 58M/T158M) ), hESC line expressing no MECP2 (MECP2-KO), congenic pair of wild-type and mutant RTT pat

178 ons differentiated from MECP2(T158M/T158M) , MECP2-KO, and V247fs-MT stem cell lines.

179 We find that mice expressing truncated MeCP2 lacking both the N- and C-terminal regions (approx

180 Defects in methyl CpG binding protein gene (MECP2) largely accounts for RTT.

181 We have shown previously that the MeCP2 level increases during differentiation and that it

182 a corrects transcriptional changes, restores MeCP2 levels and spine plasticity and ameliorates cognit

183 Genetic correction of MeCP2 levels in IL-1R8 KO neurons rescues the synaptic d

184 Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and gl

185 We show that MeCP2, like the repressive histone H1, traps the nucleos

186 signalling is upregulated in the cortex with Mecp2 loss-of-function.

187 Cx3cr1(CreER);Mecp2(fl/y)or Cx3cr1(Cr)(eER); Mecp2(LSL/y)) had little effect on excessive engulfment,

188 These data suggest that NAc core MeCP2 may be recruited by both ELS and methamphetamine S

189 ns (T158M, R106W, and P101S) destabilize the MeCP2 MBD and disrupt the recognition of mCG and mCA equ

190 al day 55, while females lacking one copy of Mecp2 (Mecp2(ZFN/+)) displayed a more protracted disease

191 Male rats lacking MeCP2 (Mecp2(ZFN/y)) were noticeably symptomatic as earl

192 ECP2(T158M/T158M) ), hESC line expressing no MECP2 (MECP2-KO), congenic pair of wild-type and mutant

193 suggest a potential mechanistic link between MeCP2-mediated transcription regulation and mGluR5/FMRP-

194 mechanistic insights into the regulation of MeCP2-mediated, higher-order chromatin architecture and

195 In the presence of the MeCP2 methyl-CpG-binding domain (MBD), however, DNA meth

196 ked neurodevelopmental disorder in which the MECP2 (methyl CpG-binding protein 2) gene is mutated.

197 We previously showed that treatment of Mecp2 mice with statin drugs alleviated motor symptoms a

198 skill, a deficit that has not been shown in Mecp2 mice.

199 Female Mecp2(+/-) mice showed a less dramatic but still substan

200 organization and binding dynamics for twelve MeCP2 missense mutations (including two novel and the fi

201 riate RNA guide to target the enzyme, 72% of Mecp2 mRNA is repaired.

202 led genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a

203 hole-cell recording of synaptic responses in MeCP2 mutant mice in vivo, we show that visually driven

204 Mecp2 mutant mice recapitulate many of the clinical feat

205 Furthermore, MeCP2 mutant mice show reduced expression of the cation-

206 pathway improves neurological phenotypes in Mecp2 mutant mice.

207 ity to detect genotype differences in female Mecp2 mutant mice.

208 Subcellular RNA analysis in MeCP2-mutant neurons further revealed reductions in the

209 of the brain impedes an understanding of how MECP2 mutations contribute to RTT.

210 ened sensitivity to sensory and social cues, Mecp2 mutations suppress adult plasticity independently

211 MECP2 mutations underlying Rett syndrome cause widesprea

212 Specific MECP2 mutations were not significantly associated with e

213 e mechanistic and phenotypic correlations of MeCP2 mutations will enable improved and individualized

214 s with clinical Rett syndrome and those with MECP2 mutations without the clinical syndrome were recru

215 iched genes were preferentially disrupted by MeCP2 mutations, with upregulated and downregulated gene

216 reatment of individuals with disease-causing MECP2 mutations.

217 We determine the cocrystal structure of the MeCP2 NID in complex with the WD40 domain of TBLR1 and c

218 Strikingly, the four MeCP2-NID residues mutated in RTT are those residues tha

219 he HG- or TGF-beta-induced upregulation of p-MeCP2, NOX4 and primary miR-25, but downregulation of pr

220 expression only in GABAergic neurons of male Mecp2 null mice enhanced inhibitory signaling, extended

221 ptic inputs at end stages of disease (>/=P56 Mecp2 null mice) concomitant with synapse loss.

222 te to pathogenesis in a RTT mouse model, the Mecp2 null mouse (Mecp2(tm1.1Bird/y)).

223 ing both MECP2 and IRAK1 Like many boys with MECP2 null mutations, this child died very early, at the

224 ouse models of MECP2 disorders (constitutive Mecp2 null, mosaic Mecp2(+/-), and MECP2 duplication): a

225 1 mimics the reduced dendritic complexity of Mecp2-null cortical callosal projection neurons (CPN), a

226 genetically reducing NF-kappaB signalling in Mecp2-null mice not only ameliorates CPN dendritic compl

227 exclusively in the somatosensory neurons of Mecp2-null mice rescues tactile sensitivity, anxiety-lik

228 24S-hydroxycholesterol (24S-OHC) found in B6.Mecp2-null mice suggests the occurrence of changes in br

229 elopment or at the onset of RTT phenotype in Mecp2-null mice.

230 y mutations in methyl-CpG-binding protein 2 (MECP2; OMIM 300005), a ubiquitously expressed factor.

231 imals, reactivation of the wild-type copy of MeCP2 on the inactive X chromosome (Xi) presents a thera

232 gene encoding the methyl-CpG-binding protein MeCP2 on the X chromosome.

233 gically suitable targets for reactivation of MeCP2 on the Xi and a genetic circuitry that maintains X

234 a single gene methyl CpG binding protein 2 (MeCP2) on the X chromosome.

235 1 (HMGD1), and methyl CpG binding protein 2 (MeCP2), on the biophysical properties of nucleosomes and

236 these features, we have found that deleting Mecp2 only from GABAergic inhibitory neurons in mice rep

237 Conversely, restoring MeCP2 only in cholinergic neurons rescued these phenotyp

238 distinct from the phenotype of mice lacking MeCP2 only in inhibitory neurons.

239 Remarkably, tactile defects resulting from Mecp2 or Gabrb3 deletion in somatosensory neurons during

240 Functions for MeCP2 other than transcriptional are not well understood

241 ynamics in Mecp2-deficient astrocytes and in MECP2 p.Arg294* iPSC-derived astrocytes in vitro.

242 Here, we show that MeCP2 plays a direct role in regulating lipid metabolism

243 (1.1% of patients) followed by CHD8, DSCAM, MECP2, POGZ, WDFY3 and ASH1L.

244 Our data suggest that HDAC3 interaction with MeCP2 positively regulates a subset of neuronal genes th

245 sorder Rett syndrome, caused by mutations in MECP2, produces a diverse array of symptoms, including l

246 Levels of MeCP2 protein are also increased significantly.

247 2 binding to methylated DNA and destabilized MeCP2 protein in an age-dependent manner, leading to the

248 antly, as in wild-type neurons, the repaired MeCP2 protein is enriched in heterochromatic foci, refle

249 MeCP2 protein is highly expressed in the nervous system

250 pite evolutionary conservation of the entire MeCP2 protein sequence, the DNA and co-repressor binding

251 The methyl-CpG-binding protein 2 (MeCP2) protein is an epigenetic reader whose binding to

252 The RTT missense MECP2(R306C) mutation prevents MeCP2 from interacting wi

253 Human RTT-patient-derived MECP2(R306C) neural progenitor cells had deficits in HDA

254 Here, we report that a novel Mecp2 rat model displays high face validity for modellin

255 ogether, these findings demonstrate that the Mecp2 rat model is a complementary tool with unique feat

256 ats and not mice, is also impaired in female Mecp2 rats.

257 Based on these findings, we suggest that MeCP2 recognition of methylated/hydroxymethylated CpA di

258 n RNA knockdown approaches to identify novel MeCP2-regulated miRNAs enriched during early human neuro

259 We show that MeCP2 regulates lipid homeostasis by anchoring the repre

260 EST, a neuronal gene repressor, mediates the MeCP2 regulation of KCC2.

261 been overlooked, we generated mice in which Mecp2 remains at near normal levels in the nervous syste

262 ry of 60,000 shRNAs using a cell line with a MeCP2 reporter on the Xi and found 30 genes clustered in

263 extended megabase-scale regions surrounding MeCP2-repressed genes.

264 e, we focus on methyl-CpG binding protein 2 (MECP2) restoration for RTT and combinatorially target fa

265 iPSC-derived neural progenitors deficient in MeCP2 restored AKT and ERK activation, respectively, and

266 omatin reorganization, which is disturbed by MeCP2 Rett syndrome mutations.

267 hippocampus-dependent learning and memory in Mecp2(+/-) (Rett) mice, also rescued all three features

268 sociation with methylation is in part due to MeCP2's affinity to GC-rich chromatin, a result replicat

269 ome-associated methyl-CpG-binding protein 2 (MeCP2) selectively binds methylated DNA to regulate tran

270 ved induced pluripotent stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify

271 Knockdown of MeCP2 shows it is instrumental for splicing and inhibits

272 To identify genes involved in MeCP2 silencing, we screened a library of 60,000 shRNAs

273 The broad tissue expression of MeCP2 suggests that it may be involved in several metabo

274 hosphorylated methyl-CpG binding protein2 (p-MeCP2) suppresses the processing of several microRNAs (m

275 uitin/proteasome pathway was responsible for MeCP2 T158M degradation and that proteasome inhibition i

276 Genetic elevation of MeCP2 T158M expression ameliorated multiple RTT-like fea

277 like phenotypes and support the targeting of MeCP2 T158M expression or stability as an alternative th

278 ion and that proteasome inhibition increased MeCP2 T158M levels.

279 , these findings demonstrate that increasing MeCP2 T158M protein expression is sufficient to mitigate

280 nts were accompanied by increased binding of MeCP2 T158M to DNA.

281 ost common RTT-associated missense mutation, MeCP2 T158M.

282 SC) line carrying the common T158M mutation (MECP2(T158M/T158M) ), hESC line expressing no MECP2 (MEC

283 REB in forebrain neurons differentiated from MECP2(T158M/T158M) , MECP2-KO, and V247fs-MT stem cell l

284 a novel miRNA-mediated pathway downstream of MeCP2 that influences neurogenesis via interactions with

285 gene encoding methyl CpG binding protein 2 (MeCP2) that occur sporadically in 1:10,000 female births

286 rder caused by loss-of-function mutations in MECP2, the gene encoding the transcriptional regulator m

287 rder caused by loss-of-function mutations in MECP2, the gene encoding the transcriptional regulator m

288 ent regulation of Sapap3 expression requires MECP2, the gene involved in the pathophysiology of Rett

289 n the absence of methyl-CpG-binding protein, MECP2, the molecular basis for cognitive decline in Rett

290 ablished that alterations in the function of MeCP2, the protein encoded by the gene mutated in Rett s

291 in a RTT mouse model, the Mecp2 null mouse (Mecp2(tm1.1Bird/y)).

292 These findings suggest a model in which MeCP2 tunes gene expression in neurons by binding within

293 n mutations in methyl-CpG-binding protein 2 (MECP2) underlie two distinct neurological syndromes with

294 lation, which, together, achieve 30,000-fold MECP2 up-regulation from the Xi in cultured cells.

295 nse mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR

296 he cerebellum of Mecp2 knockout mouse model (Mecp2 (-/y) ) during transition from the non-symptomatic

297 were apparent in Mecp2(ZFN/y) rats, whereas Mecp2(ZFN/+ )rats displayed functional irregularities la

298 Brain weights of Mecp2(ZFN/y) and Mecp2(ZFN/+ )rats were significantly reduced by postnata

299 55, while females lacking one copy of Mecp2 (Mecp2(ZFN/+)) displayed a more protracted disease course

300 Brain weights of Mecp2(ZFN/y) and Mecp2(ZFN/+ )rats were significantly re

301 and breathing abnormalities were apparent in Mecp2(ZFN/y) rats, whereas Mecp2(ZFN/+ )rats displayed f

302 Male rats lacking MeCP2 (Mecp2(ZFN/y)) were noticeably symptomatic as early as po