Li Yihong, Liu Dun, Li Zhiming, Zhang Xinhua, Ye Yuhua, Liu Qifa, Shen Jie, Chen Zhi, Huang Huajie, Liang Yunhao, Han Xu, Liu Jing, An Xiuli, Mohandas Narla, Xu Xiangmin
Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China; Reproductive Medical Center, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Blood Cells Mol Dis. 2018 Jul;71:16-22. doi: 10.1016/j.bcmd.2018.01.004. Epub 2018 Feb 15.
Erythroid Krüppel-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.
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备受关注，但仍未完全阐明。为了探究启动子 DNA 甲基化对 EKLF 表达的表观遗传调控，我们研究了一组人类组织中 EKLF 启动子的甲基化状态和 EKLF 基因表达。我们观察到，成年红系细胞中 EKLF 启动子的红系特异性低甲基化与 EKLF 表达呈正相关。5-氮杂-2'-脱氧胞苷对 EKLF 启动子的去甲基化导致非红系细胞中 EKLF 表达升高。我们进一步发现，EKLF 启动子 DNA 甲基化降低了对转录因子 GATA1 和 c-myb（MYB）的结合亲和力，进而使 EKLF 表达沉默。这些结果表明，EKLF 启动子的低甲基化在红系特异性基因表达的建立和维持中具有功能意义。
