Somatic DNA inethylation patterns are determined in part by the de novo methylation that occurs after early embryonic demethylation. Oct-314, 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-314 promoter and facilitates its methylation. Although acetylation of historic H3 at lysine 9 (K9) and/or 14 (K14) and inethylation of H3 at lysine 4 (K4) decrease during this period. Lis do Oct-314 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-314 promoter. Our finding suggests a model in which differentiation-induced GCNF recruits de novo DNA methyltransferase and facilitates the silencing of a pluripotency gene. (c) 2006 Elsevier Inc. All rights reserved.