MeCP2-dependent repression of an imprinted miR-184 released by depolarization

Nomura, Tasuku; Kimura, Masashi; Horii, Takuro; Morita, Sumiyo; Soejima, Hidenobu; Kudo, Shinichi; Hatada, Izuho

doi:10.1093/hmg/ddn011

Cited by 113 publications

(103 citation statements)

References 57 publications

(58 reference statements)

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“…MeCP2 is also involved in the regulation of neuronal genes by cooperating with REST (Ballas et al, 2005) and of the imprinted genes Dlx5 and Dlx6 (Horike et al, 2005). Recently, a brain-specific micro RNA, miR-184, was shown to be regulated by MeCP2 (Nomura et al, 2008). However, the mechanism of target gene regulation by MeCP2 is still not fully understood, and it could act by mechanisms other than the repression of transcriptional initiation (Bienvenu and Chelly, 2006).…”

Section: Functions Of the Mbd Proteins In The Nervous Systemmentioning

confidence: 99%

Many paths to one goal? The proteins that recognize methylated DNA in eukaryotes

Sasai¹,

Defossez²

2009

Int. J. Dev. Biol.

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DNA methylation is an epigenetically inherited chemical modification that is associated with transcriptional silencing and is essential for mammalian development. The DNA methylation signal is read out by methyl-CpG binding proteins (MBPs) that specifically bind to methylated DNA. Three structurally divergent families of MBPs have been identified so far: the MBD family, the SRA family and a family of proteins with Zinc fingers. In this review, we describe how the distinct families of methyl-CpG binding proteins have evolved, how they each recognize and maintain the DNA methylation mark, and finally how they turn this mark into biological effect.

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Section: Functions Of the Mbd Proteins In The Nervous Systemmentioning

confidence: 99%

Many paths to one goal? The proteins that recognize methylated DNA in eukaryotes

Sasai¹,

Defossez²

2009

Int. J. Dev. Biol.

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“…Furthermore, psychiatric disorders such as schizophrenia, autism, and Tourette's syndrome are associated with dysregulated levels of miRNAs (16)(17)(18)(19)(20). miRNAs are small (Ϸ22 nt) noncoding transcripts that can control expression of protein-coding mRNAs at the posttranscriptional level (21).…”

mentioning

confidence: 99%

MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction

Kocerha

Faghihi

López‐Toledano

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

263

216

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cerebral cortex ͉ glutamatergic signaling ͉ regulatory RNA N MDA receptors (NMDA-R) control many executive brain functions, such as working memory, and their dysfunction is implicated in a host of brain disorders (1-4). Notably, hypofunctional NMDA-R signaling, particularly in the prefrontal cortex (PFC), has been implicated in the cognitive and behavioral disturbances characteristic of schizophrenia (5), autism (6, 7), attention deficit hyperactivity disorder (ADHD) (8, 9), mood disorders (10), and other psychiatric illnesses. The cellular mechanisms by which disrupted NMDA-R transmission drives behavioral pathology are still unclear, although several of the major proteins involved in this pathway, such as calcium/calmodulin-dependent protein kinase II (CaMKII) (11), have been identified. In this study, we examine whether neurobehavioral abnormalities associated with NMDA-R hypofunction can be attributed to a novel class of regulatory RNA molecules, microRNAs (miRNAs).miRNAs have attracted much attention as regulators of neuronal development and synaptic plasticity (12-15). Furthermore, psychiatric disorders such as schizophrenia, autism, and Tourette's syndrome are associated with dysregulated levels of miRNAs (16)(17)(18)(19)(20). miRNAs are small (Ϸ22 nt) noncoding transcripts that can control expression of protein-coding mRNAs at the posttranscriptional level (21). Pleiotropic miRNAs can control gene expression by binding to complementary sequences in the 3Ј untranslated region (3Ј UTR) of target mRNA transcripts to facilitate their degradation and/or inhibit their translation (15,22,23). Understanding this layer of gene regulation therefore promises to enrich our knowledge of brain function and pathology. Dizocilpine is a highly selective phencyclidine-like NMDA-R antagonist that can rapidly produce schizophrenia-like behavioral deficits in humans and rodents (24). We examined whether a psychotomimetic dose of dizocilpine (0.5 mg/kg, i.p.) altered miRNA expression in brain regions of C57BL/6 mice, by using miRNA microarray profiling as an initial screening approach. Our analysis was focused on the PFC because of the considerable evidence linking this brain region with behavioral pathology in psychiatric illnesses (19). We extracted the small RNAs from the PFC of the mice 15 min after administration of a single dose of dizocilpine, i.e., a time-point at which dizocilpine-induced behavioral disturbances such as hyperlocomotion and stereotypy are readily observed (25). Of note, there was a robust reduction of miR-219 out of 182 miRNAs detectable by microarray in PFC tissues (Table S1). miR-219 is a conserved miRNA expressed in both rodent and human brains, but not in other tissues (26,27). These data demonstrate that concentrations of a brain-specific miRNA, which may play a role in regulating NMDA-R function, are altered during states of NMDA-R hypofunction.In support of the microarray data, RT-PCR analyses demonstrated that miR-219 levels were significantly reduced by Ϸ50% (a change from an average cycle th...

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“…Of the 58 and 35 predicted microRNA binders (for each transcript variant, National Center for Biotechnology Information [NCBI] accession nos. NM_012340 and NM_173091, respectively) identified by this query, the strongest predicted binder to the 3Ј UTR (both variants) was miR-184, a recently characterized miRNA present in a variety of tissues 35 and suggested to be of importance in DNA methylation pathways 36 and a potential antagonist of miR-205. 37 Conversely, the strongest predicted mRNA target of miR-184 (based on a reciprocal analysis of the miRNA sequence) was the previously identified sequence within the NFAT1 3Ј UTR ( Table 2).…”

Section: Ucb Cd4 ؉ T Cells Express Significantly Less Nfat1 Protein Bmentioning

confidence: 97%