ライフサイエンスコーパス: MeCP2

1 y mutations in Methyl-CpG-binding Protein 2 (MECP2).

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

3 cupancy of methylcytosine binding protein 2 (MeCP2).

4 on (FOSB, ARC, KCNJ9/GIRK3, NR4A2, JUNB, and MECP2).

5 e encoding for methyl-CpG binding-protein 2 (MeCP2).

6 ritical regulator of neuronal transcription, MeCP2.

7 ected individuals have nonsense mutations in MECP2.

8 isorder resulting from mutations in the gene MECP2.

9 ay analyses identified pathways regulated by MECP2.

10 aches must restore close to normal levels of MECP2.

11 these mice does not interfere with wild-type MeCP2.

12 d by our procedure are directly modulated by MeCP2.

13 ression were induced by transcription factor MeCP2.

14 air, delineating a pathway relationship with MECP2.

15 r deletions in Methyl-CpG-binding Protein 2 (MeCP2), a brain-enriched transcriptional regulator.

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

17 sed by hiPSC-derived neural cultures lacking MECP2, a model of the neurodevelopmental disorder Rett s

18 orders, additional systems may contribute to MeCP2 action through its target genes.

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

20 An example is MeCP2, an abundant methylated-DNA binding protein that i

21 , and in particular, the genes recognized by MeCP2 and associated to several neurological and neurops

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

23 ll as histones, and that interaction between MeCP2 and histone proteins plays a key role in gene expr

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

25 MECP2 and its product, Methyl-CpG binding protein 2 (MeC

26 Interaction between MeCP2 and methylated DNA in the regulation of gene expre

27 y (ECLIA) that is able to measure endogenous MeCP2 and recombinant TAT-MeCP2 fusion protein levels in

28 Chronic treatment of Mecp2 and Shank3 mutant mice improved body condition, so

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

30 Here, we find that genes repressed by MeCP2 are often located within megabase-scale regions of

31 is and reveal that PRC2, DNA methylation and Mecp2 are required to maintain chromosome compaction.

32 Loss-of-function mutations affecting MeCP2 are the primary cause of Rett syndrome (RTT), a se

33 d its product, Methyl-CpG binding protein 2 (MeCP2), are mostly known for their association to Rett S

34 ing studies of the kinetic features of mouse MeCP2 at high spatial-temporal resolution.

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

36 to mCG and mCAC, neither showed evidence of MeCP2 binding to GT-rich motifs.

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

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

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

40 Further, we found that MeCP2 binding to methylated miRNA loci halts RNA polymer

41 To test for MeCP2 binding to these motifs in vivo, we analysed human

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

43 ed with intellectual disability also prevent MeCP2 binding.

44 ggest a new model of MeCP2 function in which MeCP2 binds broadly across highly methylated regions of

45 nd how MeCP2 regulates transcription because MeCP2 binds broadly across the genome and MeCP2 mutation

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

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

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

49 encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT).

50 in the methyl-DNA-binding repressor protein MeCP2 cause the devastating neurodevelopmental disorder

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

52 ns in X-linked methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT).

53 rescues synaptic and behavioral deficits in Mecp2 conditional knockout mice, whereas about 12-fold d

54 MeCP2 contains several domains that contribute to the fo

55 tic insights into how non-CG methylation and MeCP2 control transcription.

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

57 However, whether MeCP2 deficiency impacts the integration of new neurons

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

59 Total knockout of P2X7Rs in MECP2 deficient mice decreases the number of inflammator

60 tamate transporter-2 signals on PV+ cells in MeCP2-deficient animals, suggesting weaker recurrent inh

61 errant excitability and network synchrony of MeCP2-deficient hippocampal neurons.

62 d synchronized firing, whereas exosomes from MECP2-deficient hiPSC neural cultures lack this capabili

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

64 Here, we report in a MECP2-deficient mouse model of RTT that the border of th

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

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

67 TT, rescued neuronal integration deficits of MeCP2-deficient neurons in vitro but not in vivo.

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

69 od to interrogate presynaptic integration of MeCP2-deficient new neurons born in the adult hippocampu

70 MECP2 deletion altered expression of 284 messenger RNAs

71 We investigated the effects of MECP2 deletion from HSCs on their transcriptome and of p

72 Mecp2 deletion in mice results in an imbalance of excita

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

74 both biochemical and genomic analyses, that MeCP2 directly interacts with nucleosomes and its genomi

75 nstead target the pathophysiology underlying MECP2 disorders.

76 MeCP2 displays dynamic features that are distinct from b

77 nhancer activity provide a mechanism for how MeCP2 disruption in disease can lead to widespread chang

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

79 Our findings argue that MeCP2 does not read unadorned DNA sequence and therefore

80 KL5-deficiency disorder, FOXG1 disorder, and MECP2 duplication disorder are developmental encephalopa

81 zure onset (2 months), whereas children with MECP2 duplication syndrome had the oldest median age at

82 hereas duplications of the MECP2 locus cause MECP2 duplication syndrome.

83 isorders and earlier age at seizure onset in MECP2 duplication syndrome.

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

85 The MeCP2 ECLIA produces highly quantitative, accurate and r

86 We propose that MeCP2 enhances the separation of heterochromatin and euc

87 Research on the mechanisms by which MeCP2 exerts effects on gene expression in neurons, stud

88 These findings suggest a new model of MeCP2 function in which MeCP2 binds broadly across highl

89 D and 3D human brain cultures to investigate MeCP2 function.

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

91 measure endogenous MeCP2 and recombinant TAT-MeCP2 fusion protein levels in a 96-well plate format.

92 of them is the use of stable and native TAT-MeCP2 fusion proteins to replenish its levels in neurons

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

94 Mutations in the MECP2 gene cause the progressive neurodevelopmental diso

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

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

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

98 opmental disorder caused by mutations in the MECP2 gene.

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

100 disorder due to pathogenic mutations in the MECP2 gene.

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

102 tations in the Methyl CpG binding protein 2 (MeCP2) gene.

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

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

105 tations in the methyl-CpG binding protein 2 (MECP2) gene.

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

107 Functionally, MeCP2 has been implicated in several cellular processes

108 ongation directly in the brain, we find that MeCP2 has no measurable effect on transcriptional elonga

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

110 Female heterozygous Mecp2 mutants (Mecp2(het) ) failed to acquire a learned maternal retrie

111 l of these neuronal changes are abolished in Mecp2(het) , suggesting that they are an essential compo

112 that restores accurate retrieval behavior in Mecp2(het) also restores maternal experience-dependent p

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

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

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

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

117 e AAV-PHP.eB to deliver an instability-prone Mecp2 (iMecp2) transgene cassette which, increasing RNA

118 We found that selective deletion of MeCP2 in adult-born new neurons impaired their long-rang

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

120 Deletion of PRC2, Dnmt1/3a/3b or Mecp2 in ESCs leads to an increase in the size of indivi

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

122 ey suggest that limited nuclear diffusion of MeCP2 in live neurons contributes to its local impact on

123 Stable binding of MeCP2 in living neurons requires its methyl-binding doma

124 as shown that re-expression of SUMO-modified MeCP2 in Mecp2-null neurons rescues synaptic and behavio

125 s is likely due to the presence of truncated MeCP2 in Mecp2R294X mice.

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

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

128 ental loss of ASD-associated genes Shank3 or Mecp2 in peripheral mechanosensory neurons leads to regi

129 We further showed that knockdown of MeCP2 in primary hippocampal neurons also resulted in re

130 are particularly vulnerable to mutations of Mecp2 in PV neurons.

131 demonstrated that the presence of truncated MeCP2 in these mice does not interfere with wild-type Me

132 ed this interaction with isolated domains of MeCP2 in vitro and defined a minimal target DNA sequence

133 Our findings indicate that MeCP2 interacts with genomic loci via binding to DNA as

134 Here we show that MeCP2 is a dynamic component of heterochromatin condensa

135 s and mathematical modeling to indicate that MeCP2 is a global transcriptional regulator whose bindin

136 Recent evidence challenges the idea that MeCP2 is a multifunctional hub that integrates diverse p

137 MeCP2 is a nuclear protein that binds to sites of cytosi

138 MeCP2 is a reader of the DNA methylome that occupies a l

139 k as the primary determinant of DNA binding, MeCP2 is also reported to have an affinity for non-methy

140 CA1 region of the hippocampus in mice where Mecp2 is deleted either in all cells or specifically in

141 Our results indicate that MeCP2 is essential for immature neurons to establish app

142 this disease presents inherent hurdles since MECP2 is expressed throughout the brain and its duplicat

143 MeCP2 is highly expressed during neuronal maturation and

144 The X-linked gene encoding MECP2 is involved in two severe and complex neurodevelop

145 These data suggest that MeCP2 is responsible for reading only part of the Dnmt3a

146 Diffusion of unbound MeCP2 is strongly constrained by weak, transient interac

147 ' of atypical non-CpG methylation (mCH), and MeCP2 is the only known 'reader' for mCH.

148 We asked if MeCP2 is the sole reader for Dnmt3a dependent methylatio

149 the gene Mecp2 Misexpression of the protein MECP2 is thought to contribute to neuropathology by caus

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

151 Methyl CpG binding protein 2 (MeCP2) is a key component of constitutive heterochromati

152 Methyl-CpG-binding protein 2 (MeCP2) is a multifunctional chromosomal protein that pla

153 Methyl-CpG-binding-Protein 2 (MeCP2) is an abundant nuclear protein highly enriched in

154 y mutations in methyl-CpG binding protein 2 (MeCP2), is one of the most prevalent intellectual disord

155 The methyl-CpG-binding protein 2 gene, MECP2, is an X chromosome-linked gene encoding the MeCP2

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

157 Treating MECP2-knockdown human primary neural cultures with contr

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

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

160 e vHIP-mPFC projection is hyperactive in the Mecp2 knockout mouse model of the autism spectrum disord

161 nsporter 3 (GAT3), in the hippocampus of the Mecp2 KO mice, as well as a corresponding increase of GA

162 ability in acute hippocampal slices from the Mecp2 KO mice.

163 e symptom score and extended lifespan in the Mecp2 KO mice.

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

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

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

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

168 58M/T158M) ), hESC line expressing no MECP2 (MECP2-KO), congenic pair of wild-type and mutant RTT pat

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

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

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

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

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

174 294X mutation introduced into the endogenous Mecp2 locus (Mecp2R294X).

175 s Rett syndrome, whereas duplications of the MECP2 locus cause MECP2 duplication syndrome.

176 avioral phenotypes observed following global Mecp2 loss of function.

177 ons and severe neurological dysfunction than MeCP2 loss.

178 Thus, MeCP2 may modulate similar mechanisms in different patho

179 Additional evidence suggests that MECP2 may underlie other neuropsychiatric and neurologic

180 s extend previous studies of the role of the MeCP2 MBD in high affinity DNA binding to living neurons

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

182 DNA methylation across the genome to dictate MeCP2-mediated enhancer regulation in the brain.

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

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

185 syndrome is caused by mutations in the gene Mecp2 Misexpression of the protein MECP2 is thought to c

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

187 tor (V1aR) and methyl CpG-binding protein 2 (MeCP2) mRNA expression, but did not alter spine density

188 mpaired in vivo cortical plasticity in awake Mecp2 mutant animals to a natural, ethologically relevan

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

190 tions underlie the abnormal transcription in MeCP2 mutant INs, which were recovered to normal levels

191 d the molecular and functional phenotypes of MeCP2 mutant INs.

192 Mecp2 mutant mice recapitulate many of the clinical feat

193 ns of the PHP.eB-iMecp2 virus in symptomatic Mecp2 mutant mice significantly improved locomotor activ

194 ne response to the transgene in treated male Mecp2 mutant mice that was overcome by immunosuppression

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

196 administration was well tolerated in female Mecp2 mutant or in wild-type animals.

197 ll-type-specific transcriptome impairment in MeCP2 mutant region-specific human brain organoids that

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

199 Female heterozygous Mecp2 mutants (Mecp2(het) ) failed to acquire a learned

200 We previously showed that female Mecp2 mutants fail to learn a simple maternal care behav

201 se MeCP2 binds broadly across the genome and MeCP2 mutations are associated with widespread small-mag

202 We found that MeCP2 mutations cause severe abnormalities in human inte

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

204 Specific MECP2 mutations were not significantly associated with e

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

206 report on the link between Rett syndrome and MECP2 mutations, it is important to reflect on the treme

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

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

209 d our results with transcriptome analysis on Mecp2-null models and cells derived from a patient with

210 that re-expression of SUMO-modified MeCP2 in Mecp2-null neurons rescues synaptic and behavioral defic

211 106 founder animals that show suppression of Mecp2-null traits from screening 3177 Mecp2/Y genomes.

212 Importantly, the impact of MeCP2 on genes differentially expressed in both models s

213 heir transcriptome and of phosphorylation of MECP2 on HSC phenotype and liver fibrosis.

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

215 We further observe that the impact of MeCP2 on transcriptional changes correlates with histone

216 In studies of mice with disruption of Mecp2 or that expressed a form of MECP2 that is not phos

217 Functions for MeCP2 other than transcriptional are not well understood

218 read-through drugs are able to suppress the Mecp2 p.R294X mutation in vivo and provide a proof of co

219 Strategies to inhibit MECP2 phosphorylation at S80 might be developed for trea

220 S80A substitution, MECP2S80, causing loss of MECP2 phosphorylation at serine 80.

221 MeCP2 plays a multifaceted role in gene expression regul

222 Levels of MeCP2 protein are also increased significantly.

223 4X mice was sufficient to elicit full-length MeCP2 protein expression in peripheral tissues.

224 Unexpectedly, full-length MeCP2 protein failed to bind GT-rich sequences in vitro.

225 to critically evaluate our understanding of MeCP2 protein function.

226 2 binding to methylated DNA and destabilized MeCP2 protein in an age-dependent manner, leading to the

227 R294X mice induced expression of full-length MeCP2 protein in the mouse brain.

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

229 ient gene transfer maintaining physiological Mecp2 protein levels in the brain.

230 l Mecp2 transgene, limits supraphysiological Mecp2 protein levels.

231 ppression agent G418 resulted in full-length MeCP2 protein production, demonstrating feasibility of t

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

233 Loss of function of the MeCP2 protein underlies Rett syndrome, whereas duplicati

234 is an X chromosome-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrom

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

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

237 In HSCs, MECP2 regulates expression of genes required for DNA rep

238 h research, the molecular mechanism by which MeCP2 regulates gene expression is not fully resolved.

239 We found that MECP2 regulates the DNA repair Fanconi anemia pathway in

240 It has been challenging to understand how MeCP2 regulates transcription because MeCP2 binds broadl

241 of extensive study because of its link with 'MECP2-related disorders', of which Rett syndrome is the

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

243 ssion occurring for enhancers located within MeCP2-repressed genes.

244 MeCP2 represses enhancers found in these domains that ar

245 We demonstrate here that MeCP2 represses nascent RNA transcription of highly meth

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

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

248 Condensates formed by MeCP2 selectively incorporate and concentrate heterochro

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

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

251 particular, the methyl-CpG-binding domain of MeCP2 shows preferential interactions with H3K27me3.

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

253 Here we find that loss of MeCP2 specifically from VIP interneurons replicates key

254 However, the widespread distribution of MeCP2 suggests it has additional interactions with chrom

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

256 s underlying EE is mediated through enhanced MeCP2 SUMOylation and increased Wnt6 expression in these

257 They also show reduced level of MeCP2 SUMOylation.

258 MeCP2 T158A mice show decreased level of GSK-3beta phosp

259 locomotor and social behavioral deficits in MeCP2 T158A mice.

260 and protein expression of BDNF and IGF-1 in MeCP2 T158A mice.

261 BDNF and IGF-1 expressions are decreased in MeCP2 T158A mice.

262 Here, we examined the role of Wnt6 in MeCP2 T158A mouse model of RTT.

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

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

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

266 ion and that proteasome inhibition increased MeCP2 T158M levels.

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

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

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

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

271 Mutations of Mecp2 that are restricted to GABAergic cell types largel

272 may be a common consequence of mutations in MeCP2 that cause Rett syndrome.

273 tudied mice that expressed a mutated form of Mecp2 that encodes the S80A substitution, MECP2S80, caus

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

275 ruption of Mecp2 or that expressed a form of MECP2 that is not phosphorylated at S80, we found phosph

276 e formation of condensates, and mutations in MECP2 that lead to Rett syndrome disrupt the ability of

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

278 critical period acceleration by deletion of MeCP2, the causative gene for Rett syndrome, despite shi

279 models of syndromic ASD (Pten(m3m4/m3m4) and Mecp2(tm1.1Bird)).

280 orylated at S80, we found phosphorylation of MECP2 to be required for HSC proliferation and induction

281 chanism by which this methylation works with MeCP2 to control gene expression is unclear.

282 lead to Rett syndrome disrupt the ability of MeCP2 to form condensates.

283 a method that uses the binding properties of MeCP2 to identify its targets, and in particular, the ge

284 etected DNA methylation-dependent binding of MeCP2 to mCG and mCAC, neither showed evidence of MeCP2

285 t can be bound by the Rett syndrome protein, MeCP2, to regulate gene expression.

286 Supplying the MECP2 transgene in Mecp2R294X mice rescued phenotypic ab

287 inefficient protein translation of the viral Mecp2 transgene, limits supraphysiological Mecp2 protein

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

289 brain tissue and study the transport of TAT-MeCP2 variants across an in vitro model of the blood-bra

290 arious transactivator of transcription (TAT)-MeCP2 variants and the development of an electrochemilum

291 Methyl-CpG binding protein 2, MECP2, which binds to methylated regions of DNA to regul

292 9 nuclease and the transcriptional regulator MeCP2, which causes Rett syndrome when mutated.

293 ations in the gene that produces the protein MECP2, which is important for changes in brain connectiv

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

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

296 We isolated HSCs from Mecp2(-/y) mice and wild-type (control) mice.

297 ion of Mecp2-null traits from screening 3177 Mecp2/Y genomes.

298 ondary mutations that improved phenotypes in Mecp2/Y mice after mutagenesis with N-ethyl-N-nitrosoure

299 Cells from Mecp2/Y mice have increased DSBs, so this finding sugges

300 ge response (DDR) also improve phenotypes in Mecp2/Y mice.