GATA Transcription Factors: Basic Principles and Related Human Disorders

GATA factor transcriptional activity: Insights from genome‐wide binding profiles

“…Heterozygous GATA2 mutations that reduce or abrogate GATA2 transcriptional activity resulted in four human syndromes often associated with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML): (a) monocytopenia/ Mycobacterium avium complex; (b) dendritic cell, monocyte, B and natural killer lymphoid deficiency; (c) Emberger's syndrome; and (d) familial MDS/AML. The first three disorders cause alterations in the immune system (i.e., low monocyte, B cell, NK cell, and dendritic cell counts) and thus indicate that GATA2 also has an important role in the development of the immune system . Activating GATA2 mutations have been identified in chronic myeloid leukemia and were also associated with an enhanced inhibitory effect on PU.1—a transcription factor essential for myeloid cell differentiation …”

“…Given its prominent role in erythroid and megakaryocytic cells, in humans GATA1 mutations cause dyserythropoietic anemia and/or thrombocytopenia, X-linked thrombocytopenia and thalassemia, and congenial erythropoietic porphyria. [53][54][55][56] Compared with wild-type GATA1, mutants unable to bind to FOG1 either have different DNA binding preferences (leading to aberrant gene expression) 14 or showed a reduced binding to regions where an association with FOG1 is required. 57 Other GATA1 mutants are associated with poor recruitment of the TAL1/LMO2 complex.…”

“…The first three disorders cause alterations in the immune system (i.e., low monocyte, B cell, NK cell, and dendritic cell counts) and thus indicate that GATA2 also has an important role in the development of the immune system. [53][54][55][56]68,69 Activating GATA2 mutations have been identified in chronic myeloid leukemia and were also associated with an enhanced inhibitory effect on PU.1-a transcription factor essential for myeloid cell differentiation. [53][54][55][56]68,69 GATA2 is also expressed in a variety of non-hematopoietic tissues (mesenchymal stem cells, endothelium, central nervous system, urogenital organs, lung, prostate, and endometrium) and cancers (lung and prostate cancers).…”

Establishment of a Screening System to Identify Novel GATA-2 Transcriptional Regulators

“…Differentiation of hematopoietic stem cells (HSCs) into specific progenitor cells, and ultimately into diverse blood cell types, is controlled by transcription factors represented by the GATA family of zinc finger DNA-binding proteins (Orkin and Zon 2008;Bresnick et al 2010;Fujiwara et al 2017). GATA-1, GATA-2, and GATA-3 are hematopoietic GATA factors, given their important roles in this process (Orkin and Zon 2008;Bresnick et al 2010;Fujiwara et al 2017).…”

“…GATA-1, GATA-2, and GATA-3 are hematopoietic GATA factors, given their important roles in this process (Orkin and Zon 2008;Bresnick et al 2010;Fujiwara et al 2017). Among them, GATA-2 is required for the maintenance and expansion of HSCs, multipotent progenitors, or both, during early hematopoiesis (Tsai et al 1994(Tsai et al , 1997Ezoe et al 2002;Rodrigues et al 2005).…”