Roles of the RUNX1 Enhancer in Normal Hematopoiesis and Leukemogenesis.
Roles of the RUNX1 Enhancer in Normal Hematopoiesis and Leukemogenesis.
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RUNX1 增强子在正常造血和白血病发生中的作用。
DOI：
10.1007/978-981-10-3233-2_10
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发表时间：
2017
影响因子：
--
通讯作者：
Sanda,Takaomi
中科院分区：
文献类型：
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作者：
Liau,Wei-Siang;Ngoc,PhuongCaoThi;Sanda,Takaomi
增强子是基因组DNA中的调控元件，包含由DNA结合转录因子结合的特定序列基序。增强子的活性以整合和组合的方式受到严格调控，从而在不同组织中产生复杂的转录模式。识别增强子对于理解其靶基因的生理和致病作用至关重要。unx1内含子增强子eR1直接调节造血干细胞（hsc）和造血内皮细胞中unx1基因的表达。RUNX1和其他造血转录因子TAL1/SCL、GATA2、PU.1、LMO2和LDB1在该区域结合。有趣的是，最近的研究表明，这个区域参与了一个被称为超级增强子的大簇增强子。在正常造血干细胞和t细胞急性淋巴母细胞白血病细胞中观察到unx1超增强子。在这篇综述中，我们描述了eR1的发现及其在正常发育和白血病发生中的作用，以及它在干细胞研究中的潜在应用。
Enhancers are regulatory elements in genomic DNA that contain specific sequence motifs that are bound by DNA-binding transcription factors. The activity of enhancers is tightly regulated in an integrated and combinatorial manner, thus yielding complex patterns of transcription in different tissues. Identifying enhancers is crucial to understanding the physiological and pathogenic roles of their target genes. TheRUNX1intronic enhancer, eR1, acts incisto regulateRUNX1gene expression in hematopoietic stem cells (HSCs) and hemogenic endothelial cells. RUNX1 and other hematopoietic transcription factors TAL1/SCL, GATA2, PU.1, LMO2 and LDB1 bind at this region. Interestingly, recent studies have revealed that this region is involved in a large cluster of enhancers termed a super-enhancer. TheRUNX1super-enhancer is observed in normal HSCs and T-cell acute lymphoblastic leukemia cells. In this review, we describe the discovery of eR1 and its roles in normal development and leukemogenesis, as well as its potential applications in stem cell research.