DNA methylation reader MECP2 : cell type- and differentiation stage-specific protein distribution

  • Background: Methyl-CpG binding protein 2 (MECP2) is a protein that specifically binds methylated DNA, thus regulating transcription and chromatin organization. Mutations in the gene have been identified as the principal cause of Rett syndrome, a severe neurological disorder. Although the role of MECP2 has been extensively studied in nervous tissues, still very little is known about its function and cell type specific distribution in other tissues. Results: Using immunostaining on tissue cryosections, we characterized the distribution of MECP2 in 60 cell types of 16 mouse neuronal and non-neuronal tissues. We show that MECP2 is expressed at a very high level in all retinal neurons except rod photoreceptors. The onset of its expression during retina development coincides with massive synapse formation. In contrast to astroglia, retinal microglial cells lack MECP2, similar to microglia in the brain, cerebellum, and spinal cord. MECP2 is also present in almost all non-neural cell types, with the exception of intestinal epithelial cells, erythropoietic cells, and hair matrix keratinocytes. Our study demonstrates the role of MECP2 as a marker of the differentiated state in all studied cells other than oocytes and spermatogenic cells. MECP2-deficient male (Mecp2−/y) mice show no apparent defects in the morphology and development of the retina. The nuclear architecture of retinal neurons is also unaffected as the degree of chromocenter fusion and the distribution of major histone modifications do not differ between Mecp2−/y and Mecp2wt mice. Surprisingly, the absence of MECP2 is not compensated by other methyl-CpG binding proteins. On the contrary, their mRNA levels were downregulated in Mecp2−/y mice. Conclusions: MECP2 is almost universally expressed in all studied cell types with few exceptions, including microglia. MECP2 deficiency does not change the nuclear architecture and epigenetic landscape of retinal cells despite the missing compensatory expression of other methyl-CpG binding proteins. Furthermore, retinal development and morphology are also preserved in Mecp2-null mice. Our study reveals the significance of MECP2 function in cell differentiation and sets the basis for future investigations in this direction.

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Metadaten
Author:Congdi Song, Yana Feodorova, Jacky Guy, Leo Peichl, Katharina Laurence Jost, Hiroshi Kimura, Maria Cristina Cardoso, Adrian Bird, Heinrich Leonhardt, Boris Joffe, Irina Solovei
URN:urn:nbn:de:hebis:30:3-345773
DOI:https://doi.org/10.1186/1756-8935-7-17
ISSN:1756-8935
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/25170345
Parent Title (English):Epigenetics & chromatin
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2014/08/03
Date of first Publication:2014/08/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/10/28
Tag:MBD; MECP2; histone modifications; mouse retina; mouse tissues; nuclear architecture; retina development
Volume:7
Issue:17
Page Number:16
Note:
© 2014 Song et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
HeBIS-PPN:366546791
Institutes:Biowissenschaften / Biowissenschaften
Angeschlossene und kooperierende Institutionen / MPI für Hirnforschung
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 4.0