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From www.bloodjournal.org by guest on June 15, 2017. For personal use only. Editorial Introduction to the review series on transcription factors in hematopoiesis and hematologic disease In this issue of Blood is a set of 6 reviews focusing on hematopoietic transcription factors. Transcription factors are DNA-binding proteins that initiate and regulate the activity of genes.1 At present, the Encyclopedia of DNA Elements (ENCODE) project has described the genome-wide occupancy of more than 150 such proteins, a subset of which have specific roles in normal and malignant hematopoiesis.2 Previously, the topic of hematopoietic transcription factors has been covered in comprehensive reviews that provide an overview of the roles of many different factors, or in focused, in-depth reviews of a single transcription factor. We recruited 6 reviews on 4 different transcription factors to create this review series. We believe that this series of reviews provides the readers of Blood with comprehensive information, while at the same time giving an in-depth look at individual transcription factors and their roles in normal and malignant hematopoiesis. Transcription factors are pleiotropic, often having different roles in different cells at different stages of development or differentiation. This is perhaps best exemplified by the transcription factor SCL/ TAL. The review provided by Porcher and colleagues3 highlights the requirement for SCL/TAL for the specification of mesoderm and eventually hematopoietic cells during development. Once hematopoiesis has begun, SCL/TAL interacts with other transcription factors to promote differentiation in maturing myeloid cells, whereas dysregulated expression of SCL/TAL leads to T-cell acute lymphoblastic leukemia. The central role of transcription factors in normal hematopoiesis and their altered expression or activity in hematologic malignancies is a recurring theme in this review series. One of the 3 members of the RUNX family of transcription factors, RUNX1 is required for the emergence of definitive hematopoietic stem cells during development and for normal stem cell function. The review by de Bruijn and Dzierzak4 traces the fundamental observations of RUNX function in normal developmental hematopoiesis and how RUNX1 performs multiple functions. The companion review by Sood and colleagues5 covers the role of RUNX factors in hematologic disease, which ranges from germ line mutations that cause familial platelet disorder with associated myeloid malignancies to acquired mutations that cause acute myeloid leukemia (AML) and many other disorders. Although SCL/TAL and RUNX affect the most primitive hematopoietic cells, other transcription factors are expressed and function mainly in specific hematopoietic lineages. The review by Avellino and Delwel6 focuses on the myeloid transcription factor, C/EPBa. In normal hematopoiesis, C/EPBa expression promotes myeloid differentiation and is critical for neutrophil maturation. An exciting aspect of this review is the mechanistic explanation of how C/EPBa expression can be altered by mutations in the CEBPA gene as well as by other oncogenes to cause AML. The GATA factors are a 6-member family of transcription factors with distinct roles at specific stages of development and in specific tissues. The review by Katsumura and Bresnick7 covers the basic biology of the GATA factors, ranging from how they interact with DNA to how GATA1 and GATA2 replace each other during hematopoietic differentiation. A highlight of this review is the focus on the interaction of GATA1 with cofactors and chromatin remodeling proteins to execute its many functions during erythropoiesis. The companion review by Crispino and Horwitz8 focuses on hematopoietic disorders that are associated with mutations in GATA1 and GATA2. Given that we are beginning to understand the pleiotropic and overlapping roles of the GATA factors in hematopoiesis, it should come as no surprise that acquired and inherited GATA mutations are associated with diverse clinical manifestations, including DiamondBlackfan anemia, acute megakaryoblastic leukemia, and congenital dyserythropoietic anemia with thrombocytopenia (GATA1), as well as myelodysplastic syndromes, AML, and blast crisis transformation in chronic myeloid leukemia (GATA2). Together these reviews highlight the fast-moving field of transcription factor biology that is reshaping our understanding of normal and malignant hematology. David M. Bodine Associate Editor, Blood References 1. Maston GA, Evans SK, Green MR. Transcriptional regulatory elements in the human genome. Annu Rev Genomics Hum Genet. 2006;7:29-59. 2. Wang J, Zhuang J, Iyer S, et al. Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors. Genome Res. 2012;22(9):1798-1812. 3. Porcher C, Chagraoui H, Kristiansen MS. SCL/TAL1: a multifaceted regulator from blood development to disease. Blood. 2017;129(15):2051-2060. 4. de Bruijn M, Dzierzak E. Runx transcription factors in the development and function of the definitive hematopoietic system. Blood. 2017;129(15):2061-2069. 5. Sood R, Kamikubo Y, Liu P. Role of RUNX1 in hematological malignancies. Blood. 2017;129(15):2070-2082. 6. Avellino R, Delwel R. Expression and regulation of C/EBPa in normal myelopoiesis and in malignant transformation. Blood. 2017;129(15):2083-2091. 7. Katsumura KR, Bresnick EH; GATA Factor Mechanisms Group. The GATA factor revolution in hematology. Blood. 2017;129(15):2092-2102. 8. Crispino JD, Horwitz MS. GATA factor mutations in hematologic disease. Blood. 2017;129(15):2103-2110. Submitted 3 February 2017; accepted 4 February 2017. Prepublished online as Blood First Edition paper, 8 February 2017; DOI 10.1182/blood-2017-02766840. BLOOD, 13 APRIL 2017 x VOLUME 129, NUMBER 15 2039 From www.bloodjournal.org by guest on June 15, 2017. For personal use only. 2017 129: 2039 doi:10.1182/blood-2017-02-766840 originally published online February 8, 2017 Introduction to the review series on transcription factors in hematopoiesis and hematologic disease David M. Bodine Updated information and services can be found at: http://www.bloodjournal.org/content/129/15/2039.full.html Articles on similar topics can be found in the following Blood collections Free Research Articles (4527 articles) Hematopoiesis and Stem Cells (3430 articles) Lymphoid Neoplasia (2557 articles) Myeloid Neoplasia (1686 articles) Phagocytes, Granulocytes, and Myelopoiesis (616 articles) Red Cells, Iron, and Erythropoiesis (794 articles) Review Series (155 articles) Information about reproducing this article in parts or in its entirety may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://www.bloodjournal.org/site/subscriptions/index.xhtml Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. 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