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DNA methylation reader MECP2 : cell type- and differentiation stage-specific protein distribution
(2014)
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.
Die Forschungsfrage dieser Arbeit untersucht die Veränderungen in der sicherheits- und verteidigungspolitischen Agenda von Bündnis 90/Die Grünen seit dem Ausbruch des Ukraine-Krieges 2022. Die Analyse zeigt, dass die Grünen ihre Agenda angepasst haben, jedoch ihre politische Kultur beibehalten. Obwohl sie sich neuen sicherheitspolitischen Herausforderungen stellen, bleiben ihre pazifistischen Grundprinzipien erhalten. Es wurde eine Reihe von Veränderungen festgestellt, darunter eine verstärkte Unterstützung für militärische Maßnahmen, jedoch bleibt die Priorität bei nicht-militärischen Ansätzen wie Diplomatie und humanitärer Hilfe. Die Ergebnisse zeigen, dass die Grünen eine pragmatischere Betrachtung der Sicherheitspolitik angenommen haben, ohne ihre grundlegenden Werte zu verlieren. Die Erkenntnisse dieser Arbeit bieten eine Grundlage für zukünftige Forschungen zur Entwicklung der sicherheitspolitischen Agenda der Grünen und zur öffentlichen Wahrnehmung dieser Veränderungen.