Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing

Harikrishnan, K N; Chow, Maggie Zi Ying; Baker, Emma K.; Pal, Sharmistha; Bassal, Sahar; Brasacchio, Daniella; Wang, Li; Craig, Jeffrey M; Jones, Peter L.; Sif, Saı̈d; El‐Osta, Assam

doi:10.1038/ng1516

Cited by 253 publications

(53 citation statements)

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“…MECP2 may also interact with other chromatin-modifying enzymes, such as histone methyltransferases, BRM, SWI/SNF, and ATRX (Fuks et al , 2003; Harikrishnan et al , 2005; Giorgio et al , 2007). Of interest, MECP2 also interacts with the DNA methyltransferase DNMT1, and thus it could be involved in the regulation of DNA methylation (Kimura and Shiota, 2003).…”

Section: Introductionmentioning

confidence: 99%

Reduced expression ofMECP2affects cell commitment and maintenance in neurons by triggering senescence: new perspective for Rett syndrome

Squillaro

Alessio

Cipollaro

et al. 2012

MBoC

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Section: Introductionmentioning

confidence: 99%

Reduced expression ofMECP2affects cell commitment and maintenance in neurons by triggering senescence: new perspective for Rett syndrome

Squillaro

Alessio

Cipollaro

et al. 2012

MBoC

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“…the Brahma subunit of the SWI/SNF complex [22], [24], [55], TFIIB, CREB1 [15], [56], RNA polymerase II, RNA splicing factor SC35 [57], H3K4 di-methylation and H4K16 acetylation and CpG methylation) ( Table 2 ). While the distribution of most of these factors or epigenetic marks was not altered by targeting MeCP2, we confirmed that MeCP2 targeting interferes with chromatin binding of linker histone H1 (FRAP data not shown), which is compatible with the observed chromatin unfolding [19], [30]–[32].…”

Section: Resultsmentioning

confidence: 99%

A Role for MeCP2 in Switching Gene Activity via Chromatin Unfolding and HP1γ Displacement

et al. 2013

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Methyl-CpG-binding protein 2 (MeCP2) is generally considered to act as a transcriptional repressor, whereas recent studies suggest that MeCP2 is also involved in transcription activation. To gain insight into this dual function of MeCP2, we assessed the impact of MeCP2 on higher-order chromatin structure in living cells using mammalian cell systems harbouring a lactose operator and reporter gene-containing chromosomal domain to assess the effect of lactose repressor-tagged MeCP2 (and separate MeCP2 domains) binding in living cells. Our data reveal that targeted binding of MeCP2 elicits extensive chromatin unfolding. MeCP2-induced chromatin unfolding is triggered independently of the methyl-cytosine-binding domain. Interestingly, MeCP2 binding triggers the loss of HP1γ at the chromosomal domain and an increased HP1γ mobility, which is not observed for HP1α and HP1β. Surprisingly, MeCP2-induced chromatin unfolding is not associated with transcriptional activation. Our study suggests a novel role for MeCP2 in reorganizing chromatin to facilitate a switch in gene activity.

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“…On the other hand, Mecp2, the responsible gene of Rett syndrome, negatively related with Fmr1 expression. It is reasonable because Mecp2 plays a role in the transcriptional repression of methylated genes including Fmr1 [20]. However, in TMD-exposed GPIN, Fmr1 was not regulated by RARs, indicating the neural induction by RA was counteracted by TMD.…”

Section: Resultsmentioning

confidence: 99%

Multi-Parametric Profiling Network Based on Gene Expression and Phenotype Data: A Novel Approach to Developmental Neurotoxicity Testing

Nagano

Akanuma

Qin

et al. 2011

IJMS

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The establishment of more efficient approaches for developmental neurotoxicity testing (DNT) has been an emerging issue for children’s environmental health. Here we describe a systematic approach for DNT using the neuronal differentiation of mouse embryonic stem cells (mESCs) as a model of fetal programming. During embryoid body (EB) formation, mESCs were exposed to 12 chemicals for 24 h and then global gene expression profiling was performed using whole genome microarray analysis. Gene expression signatures for seven kinds of gene sets related to neuronal development and neuronal diseases were selected for further analysis. At the later stages of neuronal cell differentiation from EBs, neuronal phenotypic parameters were determined using a high-content image analyzer. Bayesian network analysis was then performed based on global gene expression and neuronal phenotypic data to generate comprehensive networks with a linkage between early events and later effects. Furthermore, the probability distribution values for the strength of the linkage between parameters in each network was calculated and then used in principal component analysis. The characterization of chemicals according to their neurotoxic potential reveals that the multi-parametric analysis based on phenotype and gene expression profiling during neuronal differentiation of mESCs can provide a useful tool to monitor fetal programming and to predict developmentally neurotoxic compounds.

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Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing

Cited by 253 publications

References 50 publications

Reduced expression ofMECP2affects cell commitment and maintenance in neurons by triggering senescence: new perspective for Rett syndrome

Reduced expression ofMECP2affects cell commitment and maintenance in neurons by triggering senescence: new perspective for Rett syndrome

A Role for MeCP2 in Switching Gene Activity via Chromatin Unfolding and HP1γ Displacement

Multi-Parametric Profiling Network Based on Gene Expression and Phenotype Data: A Novel Approach to Developmental Neurotoxicity Testing

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