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A short DNA methyltransferase isoform restores methylation in vivo.

Gaudet, F. ; Talbot, D. ; Leonhardt, H. ; Jaenisch, R. (1998)
A short DNA methyltransferase isoform restores methylation in vivo.
In: The Journal of biological chemistry, 273 (49)
Artikel, Bibliographie

Kurzbeschreibung (Abstract)

Two murine DNA methyltransferase isoforms (MTases) have been observed, a longer form in somatic and embryonic stem (ES) cells and a shorter form in oocytes and preimplantation embryos. While the longer MTase is associated with maintenance methyltransferase activity in replicating cells, little is known about the shorter form. We present genetic and biochemical evidence that both isoforms are expressed from the same Dnmt1 gene by using different translation initiation sites in exons 1 and 4. We further demonstrate that the shorter isoform can functionally rescue Dnmt1 null ES cells that have a hypomethylated genome. These rescued ES cells differentiate in vivo into a variety of cell types, unlike the Dnmt1 null ES cells that die upon induction of differentiation. These results show that the shorter isoform can substitute for the longer maintenance MTase in ES and differentiated cells. Our data further indicate that the shorter MTase isoform found in oocytes is fully functional in vivo and may play an active role in the regulation of DNA methylation and the establishment of imprinting patterns.

Typ des Eintrags: Artikel
Erschienen: 1998
Autor(en): Gaudet, F. ; Talbot, D. ; Leonhardt, H. ; Jaenisch, R.
Art des Eintrags: Bibliographie
Titel: A short DNA methyltransferase isoform restores methylation in vivo.
Sprache: Englisch
Publikationsjahr: 1998
Titel der Zeitschrift, Zeitung oder Schriftenreihe: The Journal of biological chemistry
Jahrgang/Volume einer Zeitschrift: 273
(Heft-)Nummer: 49
URL / URN: http://www.cardoso-lab.org/publications/Gaudet_1998.pdf
Kurzbeschreibung (Abstract):

Two murine DNA methyltransferase isoforms (MTases) have been observed, a longer form in somatic and embryonic stem (ES) cells and a shorter form in oocytes and preimplantation embryos. While the longer MTase is associated with maintenance methyltransferase activity in replicating cells, little is known about the shorter form. We present genetic and biochemical evidence that both isoforms are expressed from the same Dnmt1 gene by using different translation initiation sites in exons 1 and 4. We further demonstrate that the shorter isoform can functionally rescue Dnmt1 null ES cells that have a hypomethylated genome. These rescued ES cells differentiate in vivo into a variety of cell types, unlike the Dnmt1 null ES cells that die upon induction of differentiation. These results show that the shorter isoform can substitute for the longer maintenance MTase in ES and differentiated cells. Our data further indicate that the shorter MTase isoform found in oocytes is fully functional in vivo and may play an active role in the regulation of DNA methylation and the establishment of imprinting patterns.

Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
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10 Fachbereich Biologie > Cell Biology and Epigenetics
Hinterlegungsdatum: 05 Mär 2010 15:46
Letzte Änderung: 24 Sep 2018 13:09
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