DNA methylation may restrict but does not determine differential gene expression at the Sgy/Tead2 locus during mouse development
DNA methylation may restrict but does not determine differential gene expression at the Sgy/Tead2 locus during mouse development
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DOI：
10.1128/mcb.24.5.1968-1982.2004
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发表时间：
2004-03-01
影响因子：
5.3
通讯作者：
DePamphilis, ML
中科院分区：
文献类型：
--
作者：
Kaneko, KJ;Rein, T;DePamphilis, ML
Soggy（Sgy）和Tead 2是两个紧密连锁的CpG岛基因，在小鼠植入前胚胎和胚胎干细胞中协同表达，但在分化细胞中差异表达。建立的细胞系的分析表明，Sgy基因的表达可以完全抑制由Sgy启动子的甲基化和DNA甲基化与染色质脱乙酰化协同作用。差异基因表达与差异DNA甲基化相关，导致在正常细胞和组织以及已建立的细胞系中开放启动子处从甲基化DNA急剧转变为非甲基化DNA。然而，在正常细胞和组织中，即使其转录物检测不到，也没有启动子甲基化。此外，Sgy启动子保持未甲基化，因为在ES细胞分化期间Sgy表达受到抑制。因此，DNA甲基化不是Sgy/Tead 2表达的主要决定因素。然而，Sgy表达始终限制在基础水平时，下游调控序列甲基化，这表明DNA甲基化限制，但不调节小鼠发育过程中的差异基因表达。
Soggy (Sgy) and Tead2, two closely linked genes with CpG islands, were coordinately expressed in mouse preimplantation embryos and embryonic stem (ES) cells but were differentially expressed in differentiated cells. Analysis of established cell lines revealed that Sgy gene expression could be fully repressed by methylation of the Sgy promoter and that DNA methylation acted synergistically with chromatin deacetylation. Differential gene expression correlated with differential DNA methylation, resulting in sharp transitions from methylated to unmethylated DNA at the open promoter in both normal cells and tissues, as well as in established cell lines. However, neither promoter was methylated in normal cells and tissues even when its transcripts were undetectable. Moreover, the Sgy promoter remained unmethylated as Sgy expression was repressed during ES cell differentiation. Therefore, DNA methylation was not the primary determinant of Sgy/Tead2 expression. Nevertheless, Sgy expression was consistently restricted to basal levels whenever downstream regulatory sequences were methylated, suggesting that DNA methylation restricts but does not regulate differential gene expression during mouse development.