Transitional CpG methylation between promoters and retroelements of tissue-specific genes during human mesenchymal cell differentiation
Transitional CpG methylation between promoters and retroelements of tissue-specific genes during human mesenchymal cell differentiation
复制标题
DOI：
10.1002/jcb.21291
复制
发表时间：
2007-09-01
影响因子：
4
通讯作者：
Rhyu, Mun-Gan
中科院分区：
文献类型：
--
作者：
Kang, Moo-Il;Kim, Hye-Soo;Rhyu, Mun-Gan
一般来说，启动子区域的甲基化与基因表达呈负相关。启动子相关的CpG岛和附近的逆转录元件之间的过渡CpG区域通常以组织特异性方式甲基化。本研究分析了人骨髓基质细胞（BMSC）和脂肪组织基质细胞（ATSC）中基因表达与过渡型CpG甲基化之间的关系，这两种细胞都具有多向分化潜能。通过甲基化特异性PCR检查了成骨细胞特异性（RUNX 2和BGLAP）、脂肪细胞特异性（PPAR γ 2）、管家基因（CDKN 2A和MLH 1）和间充质无关（RUNX 3）基因的过渡性CpGs。使用逆转录PCR分析测量每个基因的表达。BMSC中的RUNX 2、BG 4和CDKN 2A基因以及ATSC中的PPAR γ 2基因表现出过渡性CpG的低甲基化，沿着强表达。RUNX 3基因的CpG岛在BMSC和ATSC中均不表达，但甲基化程度较高。MLH 1基因的过渡性低甲基化伴随着BMSC中的表达高于ATSC。在成骨细胞分化过程中，PPAR γ 2基因的弱甲基化CpG沿着低甲基化，同时强表达。分化后除PPAR γ 2外，其他基因的过渡期甲基化和表达无明显变化。因此，在间充质细胞中建立的过渡甲基化和基因表达倾向于在分化诱导下一致地保留。BMSC中PPAR γ 2基因的弱过渡性甲基化表明骨髓脂肪生成的甲基化依赖机制。J.细胞。102：224-239，2007. (C)2007 Wiley-Liss，Inc.
In general, methylation of the promoter regions is inversely correlated with gene expression. The transitional CpG area between the promoter-associated CpG islands and the nearby retroelements is often methylated in a tissue-specific manner. This study analyzed the relationship between gene expression and the methylation of the transitional CpGs in two human stromal cells derived from the bone marrow (BMSC) and adipose tissue (ATSC), both of which have a multi lineage differentiation potential. The transitional CpGs of the osteoblast-specific (RUNX2 and BGLAP), adipocyte-specific (PPAR gamma 2), housekeeping (CDKN2A and MLH1), and mesenchyme-unrelated (RUNX3) genes were examined by methylation-specific PCR. The expression of each gene was measured using reverse-transcription PCR analysis. The RUNX2, BGLAP, and CDKN2A genes in the BMSC, and the PPAR gamma 2 gene in the ATSC exhibited hypomethylation of the transitional CpGs along with the strong expression. The CpG island of RUNX3 gene not expressed in both BMSC and ATSC was hypermethylated. Transitional hypomethylation of the MLH1 gene was accompanied by the higher expression in the BMSC than in the ATSC. The weakly methylated CpGs of the PPAR gamma 2 gene in the BMSC became hypomethylated along with the strong expression during the osteoblastic differentiation. There were no notable changes in the transitional methylation and expression of the genes other than PPAR gamma 2 after the differentiation. Therefore, the transitional methylation and gene expression established in mesenchymal cells tend to be consistently preserved under the induction of differentiation. Weak transitional methylation of the PPAR gamma 2 gene in the BMSC suggests a methylation dependent mechanism underlying the adiopogenesis of bone marrow. J. Cell. Biochem. 102: 224-239, 2007. (C) 2007 Wiley-Liss, Inc.