Analysis of the interplay between MeCP2 and histone H1 during
            <i>in vitro</i>
            differentiation of human ReNCell neural progenitor cells

Siqueira, Edilene; Kim, Bo-Hyun; Reser, Larry; Chow, Robert; Delaney, Kerry; Esteller, Manel; Ross, Mark M.; Shabanowitz, Jeffrey; Hunt, Donald F.; Guil, Sonia; Ausió, Juan

doi:10.1080/15592294.2023.2276425

Cited by 2 publications

(1 citation statement)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MeCP2 is an epigenetic factor that binds to methylated DNA in the form of both 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) [2]. Through binding to methylated DNA, MeCP2 controls gene transcription, with additional regulatory roles in RNA splicing, chromatin looping, chromatin compaction, cell signaling pathways, and protein translation [3][4][5][6][7]. Previous studies from our team have shown that the MeCP2 homeostatic regulatory pathway (MECP2-BDNF-miR132) is impaired in the post-mortem tissues of RTT patients [8].…”

Section: Introductionmentioning

confidence: 99%

Metformin Induces MeCP2 in the Hippocampus of Male Mice with Sex-Specific and Brain-Region-Dependent Molecular Impact

Arezoumand,

Roberts,

Rastegar

2024

Biomolecules

View full text Add to dashboard Cite

Rett Syndrome (RTT) is a progressive X-linked neurodevelopmental disorder with no cure. RTT patients show disease-associated symptoms within 18 months of age that include developmental regression, progressive loss of useful hand movements, and breathing difficulties, along with neurological impairments, seizures, tremor, and mental disability. Rett Syndrome is also associated with metabolic abnormalities, and the anti-diabetic drug metformin is suggested to be a potential drug of choice with few or no side-effects. Previously, we showed that in vitro exposure of metformin in a human brain cell line induces MECP2E1 transcripts, the dominant isoform of the MECP2 gene in the brain, mutations in which causes RTT. Here, we report the molecular impact of metformin in mice. Protein analysis of specific brain regions in the male and female mice by immunoblotting indicated that metformin induces MeCP2 in the hippocampus, in a sex-dependent manner. Additional experiments confirm that the regulatory role of metformin on the MeCP2 target “BDNF” is brain region-dependent and sex-specific. Measurement of the ribosomal protein S6 (in both phosphorylated and unphosphorylated forms) confirms the sex-dependent role of metformin in the liver. Our results can help foster a better understanding of the molecular impact of metformin in different brain regions of male and female adult mice, while providing some insight towards its potential in therapeutic strategies for the treatment of Rett Syndrome.

show abstract

Section: Introductionmentioning

confidence: 99%

Metformin Induces MeCP2 in the Hippocampus of Male Mice with Sex-Specific and Brain-Region-Dependent Molecular Impact

Arezoumand,

Roberts,

Rastegar

2024

Biomolecules

View full text Add to dashboard Cite

show abstract

Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms

Kalani,

Kim,

de Chavez

et al. 2024

Human Molecular Genetics

View full text Add to dashboard Cite

Mutations in methyl-CpG binding protein 2 (MeCP2), such as the T158M, P152R, R294X, and R306C mutations, are responsible for most Rett syndrome (RTT) cases. These mutations often result in altered protein expression that appears to correlate with changes in the nuclear size; however, the molecular details of these observations are poorly understood. Using a C2C12 cellular system expressing human MeCP2-E1 isoform as well as mouse models expressing these mutations, we show that T158M and P152R result in a decrease in MeCP2 protein, whereas R306C has a milder variation, and R294X resulted in an overall 2.5 to 3 fold increase. We also explored the potential involvement of the MeCP2 PEST domains in the proteasome-mediated regulation of MeCP2. Finally, we used the R294X mutant to gain further insight into the controversial competition between MeCP2 and histone H1 in the chromatin context. Interestingly, in R294X, MeCP2 E1 and E2 isoforms were differently affected, where the E1 isoform contributes to much of the overall protein increase observed, while E2 decreases by half. The modes of MeCP2 regulation, thus, appear to be differently regulated in the two isoforms.

show abstract

Analysis of the interplay between MeCP2 and histone H1 during in vitro differentiation of human ReNCell neural progenitor cells

Cited by 2 publications

References 93 publications

Metformin Induces MeCP2 in the Hippocampus of Male Mice with Sex-Specific and Brain-Region-Dependent Molecular Impact

Metformin Induces MeCP2 in the Hippocampus of Male Mice with Sex-Specific and Brain-Region-Dependent Molecular Impact

Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms

Contact Info

Product

Resources

About