Role of tissue-specific promoter DNA methylation in regulating the human EKLF gene
Role of tissue-specific promoter DNA methylation in regulating the human EKLF gene
复制标题
组织特异性启动子 DNA 甲基化在调节人 EKLF 基因中的作用
DOI：
10.1016/j.bcmd.2018.01.004
复制
发表时间：
2018-07-01
影响因子：
2.3
通讯作者：
Xu, Xiangmin
中科院分区：
文献类型：
--
作者：
Li, Yihong;Liu, Dun;Xu, Xiangmin
红系kruppel样因子（EKLF/KLF1）是一种红系特异性转录因子，其活性对红细胞生成至关重要。EKLF特异性局限于红系细胞的潜在机制引起了极大的兴趣，但仍未完全了解。为了探索启动子DNA甲基化对EKLF表达的表观遗传调控，我们从一组人体组织中研究了EKLF启动子的甲基化状态和EKLF基因的表达。我们观察到，成人红细胞中EKLF启动子的红细胞特异性低甲基化与EKLF表达呈正相关。5-aza-2'-脱氧胞苷对EKLF启动子的去甲基化导致EKLF在非红细胞中的表达升高。我们进一步发现，EKLF启动子DNA甲基化降低了转录因子GATA1和c-myb （MYB）的结合亲和力，从而沉默了EKLF的表达。这些结果表明，EKLF启动子的低甲基化在红细胞特异性基因表达的建立和维持中具有功能意义。
Erythroid Kruppel-like factor (EKLF/KLF1) is an erythroid-specific transcription factor whose activity is essential for erythropoiesis. The underlying mechanisms for EKLF specifically restricted to erythroid cells are of great interest but remain incompletely understood. To explore the epigenetic regulation of EKLF expression by promoter DNA methylation, we investigated the methylation status of the EKLF promoter and EKLF gene expression from a panel of human tissues. We observed that erythroid-specific hypomethylation of the EKLF promoter in adult erythroid cells was positively associated with EKLF expression. Demethylation of the EKLF promoter by 5-aza-2'-deoxycytidine led to elevated EKLF expression in non-erythroid cells. We further uncovered that EKLF promoter DNA methylation reduced the binding affinity for the transcription factors GATA1 and c-myb (MYB), which in turn silenced EKLF expression. These results suggest that hypomethylation of the EKLF promoter has functional significance in the establishment and maintenance of erythroid-specific gene expression.