MeCP2 and the enigmatic organization of brain chromatin. Implications for depression and cocaine addiction

Ausió, Juan

doi:10.1186/s13148-016-0214-5

Cited by 39 publications

(30 citation statements)

References 165 publications

(214 reference statements)

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“…Interestingly, MBD is the only structured domain (α-helix) while 60% of MECP2 is unstructured [39]. There are several post translational modifications of MECP2 known which contribute to its multi-functional properties, phosphorylation, acetylation, SUMOylation, and ubiquitination [41]. …”

Section: Mecp2 Gene Transcript and Proteinmentioning

confidence: 99%

Rett syndrome – biological pathways leading from MECP2 to disorder phenotypes

Ehrhart

Coort

Cirillo

et al. 2016

Orphanet J Rare Dis

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Rett syndrome (RTT) is a rare disease but still one of the most abundant causes for intellectual disability in females. Typical symptoms are onset at month 6–18 after normal pre- and postnatal development, loss of acquired skills and severe intellectual disability. The type and severity of symptoms are individually highly different. A single mutation in one gene, coding for methyl-CpG-binding protein 2 (MECP2), is responsible for the disease. The most important action of MECP2 is regulating epigenetic imprinting and chromatin condensation, but MECP2 influences many different biological pathways on multiple levels although the molecular pathways from gene to phenotype are currently not fully understood. In this review the known changes in metabolite levels, gene expression and biological pathways in RTT are summarized, discussed how they are leading to some characteristic RTT phenotypes and therefore the gaps of knowledge are identified. Namely, which phenotypes have currently no mechanistic explanation leading back to MECP2 related pathways? As a result of this review the visualization of the biologic pathways showing MECP2 up- and downstream regulation was developed and published on WikiPathways which will serve as template for future omics data driven research. This pathway driven approach may serve as a use case for other rare diseases, too.

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Section: Mecp2 Gene Transcript and Proteinmentioning

confidence: 99%

Rett syndrome – biological pathways leading from MECP2 to disorder phenotypes

Ehrhart

Coort

Cirillo

et al. 2016

Orphanet J Rare Dis

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“…Methyl CpG binding protein 2 (MeCP2) is a basic DNA binding protein with preference for methylated DNA 1,2 and is highly abundant in the brain. 3 This protein functions as a transcriptional regulator by virtue of its interaction with both transcription activator and repressor complexes.…”

Section: Introductionmentioning

confidence: 99%

Trichostatin A decreases the levels of MeCP2 expression and phosphorylation and increases its chromatin binding affinity

et al. 2017

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MeCP2 binds to methylated DNA in a chromatin context and has an important role in cancer and brain development and function. Histone deacetylase (HDAC) inhibitors are currently being used to palliate many cancer and neurological disorders. Yet, the molecular mechanisms involved are not well known for the most part and, in particular, the relationship between histone acetylation and MeCP2 is not well understood. In this paper, we study the effect of the HDAC inhibitor trichostatin A (TSA) on MeCP2, a protein whose dysregulation plays an important role in these diseases. We find that treatment of cells with TSA decreases the phosphorylation state of this protein and appears to result in a higher MeCP2 chromatin binding affinity. Yet, the binding dynamics with which the protein binds to DNA appear not to be significantly affected despite the chromatin reorganization resulting from the high levels of acetylation. HDAC inhibition also results in an overall decrease in MeCP2 levels of different cell lines. Moreover, we show that miR132 increases upon TSA treatment, and is one of the players involved in the observed downregulation of MeCP2.

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“…(C) Behavior: Although prolactin is most directly associated with lactation and some aspects of maternal behavior [128], the other pathways involved in prolactin release should also be considered when analyzing the effects of buprenorphine ( Figure 6E and Supplementary Materials Table S23). One of the key feedback pathways involved in prolactin release is dopamine release from the hypothalamus [130], as high dopamine levels exert an inhibitory effect on the release of prolactin [131]. The fact that buprenorphine can both increase or decrease prolactin levels supports the hypothesis that it interacts with the dopaminergic systems of the brain, and, also supporting this conclusion, it has been demonstrated that buprenorphine exposure affects the dopamine receptor density in the striatum [123].…”

Section: Buprenorphine: Opioidmentioning

confidence: 79%

“…Buprenorphine has also been suspected to act at an epigenetic level [147,148], as it has been linked with changes in gene expression of the methyl-DNA binding protein MeCP2, an important regulator of brain development, as well as several histone PTMs ( [131,149], Georgel's laboratory, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Potential Health Risks Linked to Emerging Contaminants in Major Rivers and Treated Waters

Kessler

Dawley

Crow

et al. 2019

Water

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The presence of endocrine-disrupting chemicals (EDCs) in our local waterways is becoming an increasing threat to the surrounding population. These compounds and their degradation products (found in pesticides, herbicides, and plastic waste) are known to interfere with a range of biological functions from reproduction to differentiation. To better understand these effects, we used an in silico ontological pathway analysis to identify the genes affected by the most commonly detected EDCs in large river water supplies, which we grouped together based on four common functions: Organismal injuries, cell death, cancer, and behavior. In addition to EDCs, we included the opioid buprenorphine in our study, as this similar ecological threat has become increasingly detected in river water supplies. Through the identification of the pleiotropic biological effects associated with both the acute and chronic exposure to EDCs and opioids in local water supplies, our results highlight a serious health threat worthy of additional investigations with a potential emphasis on the effects linked to increased DNA damage.

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MeCP2 and the enigmatic organization of brain chromatin. Implications for depression and cocaine addiction

Cited by 39 publications

References 165 publications

Rett syndrome – biological pathways leading from MECP2 to disorder phenotypes

Rett syndrome – biological pathways leading from MECP2 to disorder phenotypes

Trichostatin A decreases the levels of MeCP2 expression and phosphorylation and increases its chromatin binding affinity

Potential Health Risks Linked to Emerging Contaminants in Major Rivers and Treated Waters

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