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Coordinate regulation of DNA methyltransferase expression during oogenesis

BACKGROUND: Normal mammalian development requires the action of DNA methyltransferases (DNMTs) for the establishment and maintenance of DNA methylation within repeat elements and imprinted genes. Here we report the expression dynamics of Dnmt3a and Dnmt3b, as well as a regulator of DNA methylation,...

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Autores principales: Lucifero, Diana, La Salle, Sophie, Bourc'his, Déborah, Martel, Josée, Bestor, Timothy H, Trasler, Jacquetta M
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1878483/
https://www.ncbi.nlm.nih.gov/pubmed/17445268
http://dx.doi.org/10.1186/1471-213X-7-36
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author Lucifero, Diana
La Salle, Sophie
Bourc'his, Déborah
Martel, Josée
Bestor, Timothy H
Trasler, Jacquetta M
author_facet Lucifero, Diana
La Salle, Sophie
Bourc'his, Déborah
Martel, Josée
Bestor, Timothy H
Trasler, Jacquetta M
author_sort Lucifero, Diana
collection PubMed
description BACKGROUND: Normal mammalian development requires the action of DNA methyltransferases (DNMTs) for the establishment and maintenance of DNA methylation within repeat elements and imprinted genes. Here we report the expression dynamics of Dnmt3a and Dnmt3b, as well as a regulator of DNA methylation, Dnmt3L, in isolated female germ cells. RESULTS: Our results indicate that these enzymes are coordinately regulated and that their expression peaks during the stage of postnatal oocyte development when maternal methylation imprints are established. We find that Dnmt3a, Dnmt3b, Dnmt3L and Dnmt1o transcript accumulation is related to oocyte diameter. Furthermore, DNMT3L deficient 15 dpp oocytes have aberrantly methylated Snrpn, Peg3 and Igf2r DMRs, but normal IAP and LINE-1 methylation levels, thereby highlighting a male germ cell specific role for DNMT3L in the establishment of DNA methylation at repeat elements. Finally, real-time RT-PCR analysis indicates that the depletion of either DNMT3L or DNMT1o in growing oocytes results in the increased expression of the de novo methyltransferase Dnmt3b, suggesting a potential compensation mechanism by this enzyme for the loss of one of the other DNA methyltransferases. CONCLUSION: Together these results provide a better understanding of the developmental regulation of Dnmt3a, Dnmt3b and Dnmt3L at the time of de novo methylation during oogenesis and demonstrate that the involvement of DNMT3L in retrotransposon silencing is restricted to the male germ line. This in turn suggests the existence of other factors in the oocyte that direct DNA methylation to transposons.
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spelling pubmed-18784832007-05-29 Coordinate regulation of DNA methyltransferase expression during oogenesis Lucifero, Diana La Salle, Sophie Bourc'his, Déborah Martel, Josée Bestor, Timothy H Trasler, Jacquetta M BMC Dev Biol Research Article BACKGROUND: Normal mammalian development requires the action of DNA methyltransferases (DNMTs) for the establishment and maintenance of DNA methylation within repeat elements and imprinted genes. Here we report the expression dynamics of Dnmt3a and Dnmt3b, as well as a regulator of DNA methylation, Dnmt3L, in isolated female germ cells. RESULTS: Our results indicate that these enzymes are coordinately regulated and that their expression peaks during the stage of postnatal oocyte development when maternal methylation imprints are established. We find that Dnmt3a, Dnmt3b, Dnmt3L and Dnmt1o transcript accumulation is related to oocyte diameter. Furthermore, DNMT3L deficient 15 dpp oocytes have aberrantly methylated Snrpn, Peg3 and Igf2r DMRs, but normal IAP and LINE-1 methylation levels, thereby highlighting a male germ cell specific role for DNMT3L in the establishment of DNA methylation at repeat elements. Finally, real-time RT-PCR analysis indicates that the depletion of either DNMT3L or DNMT1o in growing oocytes results in the increased expression of the de novo methyltransferase Dnmt3b, suggesting a potential compensation mechanism by this enzyme for the loss of one of the other DNA methyltransferases. CONCLUSION: Together these results provide a better understanding of the developmental regulation of Dnmt3a, Dnmt3b and Dnmt3L at the time of de novo methylation during oogenesis and demonstrate that the involvement of DNMT3L in retrotransposon silencing is restricted to the male germ line. This in turn suggests the existence of other factors in the oocyte that direct DNA methylation to transposons. BioMed Central 2007-04-19 /pmc/articles/PMC1878483/ /pubmed/17445268 http://dx.doi.org/10.1186/1471-213X-7-36 Text en Copyright © 2007 Lucifero et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lucifero, Diana
La Salle, Sophie
Bourc'his, Déborah
Martel, Josée
Bestor, Timothy H
Trasler, Jacquetta M
Coordinate regulation of DNA methyltransferase expression during oogenesis
title Coordinate regulation of DNA methyltransferase expression during oogenesis
title_full Coordinate regulation of DNA methyltransferase expression during oogenesis
title_fullStr Coordinate regulation of DNA methyltransferase expression during oogenesis
title_full_unstemmed Coordinate regulation of DNA methyltransferase expression during oogenesis
title_short Coordinate regulation of DNA methyltransferase expression during oogenesis
title_sort coordinate regulation of dna methyltransferase expression during oogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1878483/
https://www.ncbi.nlm.nih.gov/pubmed/17445268
http://dx.doi.org/10.1186/1471-213X-7-36
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