Kaneko Kotaro J, Rein Theo, Guo Zong-Sheng, Latham Keith, DePamphilis Melvin L
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2753, USA.
Mol Cell Biol. 2004 Mar;24(5):1968-82. doi: 10.1128/MCB.24.5.1968-1982.2004.
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.
Soggy（Sgy）和Tead2是两个紧密相连且带有CpG岛的基因，它们在小鼠植入前胚胎和胚胎干细胞（ES细胞）中协同表达，但在分化细胞中差异表达。对已建立细胞系的分析表明，Sgy基因的表达可通过Sgy启动子的甲基化被完全抑制，并且DNA甲基化与染色质去乙酰化协同作用。差异基因表达与差异DNA甲基化相关，在正常细胞、组织以及已建立的细胞系中，开放启动子处的DNA从甲基化状态到未甲基化状态都有明显转变。然而，即使在正常细胞和组织中其转录本无法检测到，两个启动子也都未发生甲基化。此外，在ES细胞分化过程中，随着Sgy表达被抑制，Sgy启动子仍保持未甲基化状态。因此，DNA甲基化不是Sgy/Tead2表达的主要决定因素。尽管如此，每当下游调控序列发生甲基化时，Sgy的表达始终被限制在基础水平，这表明DNA甲基化在小鼠发育过程中限制但不调控差异基因表达。
