Ludwig, Anne K. ; Zhang, Peng ; Hastert, Florian D. ; Meyer, Stephanie ; Rausch, Cathia ; Herce, Henry D. ; Müller, Udo ; Lehmkuhl, Anne ; Hellmann, Ines ; Trummer, Carina ; Storm, Christian ; Leonhardt, Heinrich ; Cardoso, M. Cristina (2017)
Binding of MBD proteins to DNA blocks Tet1 function thereby modulating transcriptional noise.
In: Nucleic acids research, 45 (5)
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
Aberrant DNA methylation is a hallmark of various human disorders, indicating that the spatial and temporal regulation of methylation readers and modifiers is imperative for development and differentiation. In particular, the cross-regulation between 5-methylcytosine binders (MBD) and modifiers (Tet) has not been investigated. Here, we show that binding of Mecp2 and Mbd2 to DNA protects 5-methylcytosine from Tet1-mediated oxidation. The mechanism is not based on competition for 5-methylcytosine binding but on Mecp2 and Mbd2 directly restricting Tet1 access to DNA. We demonstrate that the efficiency of this process depends on the number of bound MBDs per DNA molecule. Accordingly, we find 5-hydroxymethylcytosine enriched at heterochromatin of Mecp2-deficient neurons of a mouse model for Rett syndrome and Tet1-induced reexpression of silenced major satellite repeats. These data unveil fundamental regulatory mechanisms of Tet enzymes and their potential pathophysiological role in Rett syndrome. Importantly, it suggests that Mecp2 and Mbd2 have an essential physiological role as guardians of the epigenome.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2017 |
| Autor(en): | Ludwig, Anne K. ; Zhang, Peng ; Hastert, Florian D. ; Meyer, Stephanie ; Rausch, Cathia ; Herce, Henry D. ; Müller, Udo ; Lehmkuhl, Anne ; Hellmann, Ines ; Trummer, Carina ; Storm, Christian ; Leonhardt, Heinrich ; Cardoso, M. Cristina |
| Art des Eintrags: | Bibliographie |
| Titel: | Binding of MBD proteins to DNA blocks Tet1 function thereby modulating transcriptional noise. |
| Sprache: | Englisch |
| Publikationsjahr: | 2017 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Nucleic acids research |
| Jahrgang/Volume einer Zeitschrift: | 45 |
| (Heft-)Nummer: | 5 |
| Kurzbeschreibung (Abstract): | Aberrant DNA methylation is a hallmark of various human disorders, indicating that the spatial and temporal regulation of methylation readers and modifiers is imperative for development and differentiation. In particular, the cross-regulation between 5-methylcytosine binders (MBD) and modifiers (Tet) has not been investigated. Here, we show that binding of Mecp2 and Mbd2 to DNA protects 5-methylcytosine from Tet1-mediated oxidation. The mechanism is not based on competition for 5-methylcytosine binding but on Mecp2 and Mbd2 directly restricting Tet1 access to DNA. We demonstrate that the efficiency of this process depends on the number of bound MBDs per DNA molecule. Accordingly, we find 5-hydroxymethylcytosine enriched at heterochromatin of Mecp2-deficient neurons of a mouse model for Rett syndrome and Tet1-induced reexpression of silenced major satellite repeats. These data unveil fundamental regulatory mechanisms of Tet enzymes and their potential pathophysiological role in Rett syndrome. Importantly, it suggests that Mecp2 and Mbd2 have an essential physiological role as guardians of the epigenome. |
| ID-Nummer: | pmid:27923996 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Vegetationsökologie und Restitution 10 Fachbereich Biologie > Cell Biology and Epigenetics |
| Hinterlegungsdatum: | 04 Jan 2017 11:01 |
| Letzte Änderung: | 19 Apr 2017 12:22 |
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