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Publication : The orphan nuclear receptor GCNF recruits DNA methyltransferase for Oct-3/4 silencing.

First Author  Sato N Year  2006
Journal  Biochem Biophys Res Commun Volume  344
Issue  3 Pages  845-51
PubMed ID  16631596 Mgi Jnum  J:108536
Mgi Id  MGI:3624214 Doi  10.1016/j.bbrc.2006.04.007
Citation  Sato N, et al. (2006) The orphan nuclear receptor GCNF recruits DNA methyltransferase for Oct-3/4 silencing. Biochem Biophys Res Commun 344(3):845-51
abstractText  Somatic DNA methylation patterns are determined in part by the de novo methylation that occurs after early embryonic demethylation. Oct-3/4, a pluripotency gene, is unmethylated in the blastocyst, but undergoes de novo methylation and silencing during gastrulation. Here we show that the transcriptional repressor GCNF recruits DNA methyltransferase to the Oct-3/4 promoter and facilitates its methylation. Although acetylation of histone H3 at lysine 9 (K9) and/or 14 (K14) and methylation of H3 at lysine 4 (K4) decrease during this period, as do Oct-3/4 transcript levels, H3K9 and H3K27 methylation levels remain constant, indicating that DNA methylation does not require repressive histone modifications. We found that GCNF interacts directly with Dnmt3 molecule(s) and verified that this interaction induces the methylation of the Oct-3/4 promoter. Our finding suggests a model in which differentiation-induced GCNF recruits de novo DNA methyltransferase and facilitates the silencing of a pluripotency gene.
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