Liau Wei-Siang, Ngoc Phuong Cao Thi, Sanda Takaomi
Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore.
Adv Exp Med Biol. 2017;962:139-147. doi: 10.1007/978-981-10-3233-2_10.
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. The RUNX1 intronic enhancer, eR1, acts in cis to regulate RUNX1 gene 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. The RUNX1 super-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.
增强子是基因组DNA中的调控元件，包含特定的序列基序，可被DNA结合转录因子结合。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。鉴定增强子对于理解其靶基因的生理和致病作用至关重要。RUNX1内含子增强子eR1顺式作用于造血干细胞（HSC）和造血内皮细胞中RUNX1基因的表达。RUNX1和其他造血转录因子TAL1/SCL、GATA2、PU.1、LMO2和LDB1结合在该区域。有趣的是，最近的研究表明，该区域参与了一大群被称为超级增强子的增强子。在正常造血干细胞和T细胞急性淋巴细胞白血病细胞中观察到RUNX1超级增强子。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，以及其在干细胞研究中的潜在应用。
