title: DNA methylation reader MECP2: cell type- and differentiation stage-specific protein distribution.
abstract: 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 Mecp2 (wt) 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.
authors.affiliation: Department of Biology II, Center for Integrated Protein Science Munich (CIPSM), Ludwig Maximilians University Munich, Grosshadernerstrasse 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Congdi
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Biology II, Center for Integrated Protein Science Munich (CIPSM), Ludwig Maximilians University Munich, Grosshadernerstrasse 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Yana
authors.initials: Y
authors.lastname: Feodorova
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, EH9 3JR Edinburgh, UK.
authors.forename: Jacky
authors.initials: J
authors.lastname: Guy
authors.affiliation: Max Planck Institute for Brain Research, Max-von-Laue-Str. 4, Frankfurt am Main 60438, Germany.
authors.forename: Leo
authors.initials: L
authors.lastname: Peichl
authors.affiliation: Cell Biology and Epigenetics, Department of Biology, Technische Universität Darmstadt, Schnittspahnstr. 10, Darmstadt 64287, Germany.
authors.forename: Katharina Laurence
authors.initials: KL
authors.lastname: Jost
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, 565-0871 Suita, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Cell Biology and Epigenetics, Department of Biology, Technische Universität Darmstadt, Schnittspahnstr. 10, Darmstadt 64287, Germany.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Cardoso
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, EH9 3JR Edinburgh, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Bird
authors.affiliation: Department of Biology II, Center for Integrated Protein Science Munich (CIPSM), Ludwig Maximilians University Munich, Grosshadernerstrasse 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Leonhardt
authors.affiliation: Department of Biology II, Center for Integrated Protein Science Munich (CIPSM), Ludwig Maximilians University Munich, Grosshadernerstrasse 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Joffe
authors.affiliation: Department of Biology II, Center for Integrated Protein Science Munich (CIPSM), Ludwig Maximilians University Munich, Grosshadernerstrasse 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Solovei
keywords: Histone modifications; MBD; MECP2; Mouse retina; Mouse tissues; Nuclear architecture; Retina development