title: Roles of the RUNX1 Enhancer in Normal Hematopoiesis and Leukemogenesis.
abstract: 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.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
authors.forename: Wei-Siang
authors.initials: WS
authors.lastname: Liau
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
authors.forename: Phuong Cao Thi
authors.initials: PC
authors.lastname: Ngoc
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore. takaomi_sanda@nus.edu.sg.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore. takaomi_sanda@nus.edu.sg.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Sanda
mesh_terms: D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D014157:Transcription Factors
keywords: Hematopoietic stem cells; RUNX1; Super-enhancer; T-ALL; eR1