Methyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders

Abstract MECP2 and its product, Methyl-CpG binding protein 2 (MeCP2), are mostly known for their association to Rett Syndrome (RTT), a rare neurodevelopmental disorder. Additional evidence suggests that MECP2 may underlie other neuropsychiatric and neurological conditions, and perhaps modulate commo...

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Autores principales:	Snow Bach, Niamh M. Ryan, Paolo Guasoni, Aiden P. Corvin, Rania A. El-Nemr, Danyal Khan, Albert Sanfeliu, Daniela Tropea
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/892f713a12fe47c58b87bf791fac1f20
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spelling	oai:doaj.org-article:892f713a12fe47c58b87bf791fac1f202021-12-02T13:33:59ZMethyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders10.1038/s41598-020-79268-02045-2322https://doaj.org/article/892f713a12fe47c58b87bf791fac1f202020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79268-0https://doaj.org/toc/2045-2322Abstract MECP2 and its product, Methyl-CpG binding protein 2 (MeCP2), are mostly known for their association to Rett Syndrome (RTT), a rare neurodevelopmental disorder. Additional evidence suggests that MECP2 may underlie other neuropsychiatric and neurological conditions, and perhaps modulate common presentations and pathophysiology across disorders. To clarify the mechanisms of these interactions, we develop a method that uses the binding properties of MeCP2 to identify its targets, and in particular, the genes recognized by MeCP2 and associated to several neurological and neuropsychiatric disorders. Analysing mechanisms and pathways modulated by these genes, we find that they are involved in three main processes: neuronal transmission, immuno-reactivity, and development. Also, while the nervous system is the most relevant in the pathophysiology of the disorders, additional systems may contribute to MeCP2 action through its target genes. We tested our results with transcriptome analysis on Mecp2-null models and cells derived from a patient with RTT, confirming that the genes identified by our procedure are directly modulated by MeCP2. Thus, MeCP2 may modulate similar mechanisms in different pathologies, suggesting that treatments for one condition may be effective for related disorders.Snow BachNiamh M. RyanPaolo GuasoniAiden P. CorvinRania A. El-NemrDanyal KhanAlbert SanfeliuDaniela TropeaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Snow Bach Niamh M. Ryan Paolo Guasoni Aiden P. Corvin Rania A. El-Nemr Danyal Khan Albert Sanfeliu Daniela Tropea Methyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders
description	Abstract MECP2 and its product, Methyl-CpG binding protein 2 (MeCP2), are mostly known for their association to Rett Syndrome (RTT), a rare neurodevelopmental disorder. Additional evidence suggests that MECP2 may underlie other neuropsychiatric and neurological conditions, and perhaps modulate common presentations and pathophysiology across disorders. To clarify the mechanisms of these interactions, we develop a method that uses the binding properties of MeCP2 to identify its targets, and in particular, the genes recognized by MeCP2 and associated to several neurological and neuropsychiatric disorders. Analysing mechanisms and pathways modulated by these genes, we find that they are involved in three main processes: neuronal transmission, immuno-reactivity, and development. Also, while the nervous system is the most relevant in the pathophysiology of the disorders, additional systems may contribute to MeCP2 action through its target genes. We tested our results with transcriptome analysis on Mecp2-null models and cells derived from a patient with RTT, confirming that the genes identified by our procedure are directly modulated by MeCP2. Thus, MeCP2 may modulate similar mechanisms in different pathologies, suggesting that treatments for one condition may be effective for related disorders.
format	article
author	Snow Bach Niamh M. Ryan Paolo Guasoni Aiden P. Corvin Rania A. El-Nemr Danyal Khan Albert Sanfeliu Daniela Tropea
author_facet	Snow Bach Niamh M. Ryan Paolo Guasoni Aiden P. Corvin Rania A. El-Nemr Danyal Khan Albert Sanfeliu Daniela Tropea
author_sort	Snow Bach
title	Methyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders
title_short	Methyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders
title_full	Methyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders
title_fullStr	Methyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders
title_full_unstemmed	Methyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders
title_sort	methyl-cpg-binding protein 2 mediates overlapping mechanisms across brain disorders
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/892f713a12fe47c58b87bf791fac1f20
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Methyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders

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