The orphan nuclear receptor GCNF recruits DNA methyltransferase for Oct-3/4 silencing.
The orphan nuclear receptor GCNF recruits DNA methyltransferase for Oct-3/4 silencing.
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DOI：
10.1016/j.bbrc.2006.04.007
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发表时间：
2006-06
影响因子：
3.1
通讯作者：
N. Sato;Mitsumasa Kondo;K. Arai
中科院分区：
文献类型：
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作者：
N. Sato;Mitsumasa Kondo;K. Arai
体细胞DNA甲基化模式部分由早期胚胎去甲基化后发生的从头甲基化决定。Oct-3/4是一个多能性基因，在胚泡中未甲基化，但在原肠胚形成期间经历从头甲基化和沉默。在这里，我们表明，转录抑制因子GCNF招募DNA甲基转移酶的Oct-3/4启动子，并促进其甲基化。虽然组蛋白H3在赖氨酸9（K9）和/或14（K14）的乙酰化和H3在赖氨酸4（K4）的甲基化在此期间减少，Oct-3/4转录水平，H3 K9和H3 K27甲基化水平保持不变，表明DNA甲基化不需要抑制性组蛋白修饰。我们发现GCNF直接与Dnmt 3分子相互作用，并证实这种相互作用诱导Oct-3/4启动子的甲基化。我们的研究结果表明，分化诱导的GCNF招募从头DNA甲基转移酶和促进沉默的多能性基因的模型。
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.