title: GATA-related hematologic disorders.
abstract: The transcription factors GATA1 and GATA2 are fundamental regulators of hematopoiesis and have overlapping expression profiles. GATA2 is expressed in hematopoietic stem cells and early erythroid-megakaryocytic progenitors and activates a certain set of early-phase genes, including the GATA2 gene itself. GATA2 also initiates GATA1 gene expression. In contrast, GATA1 is expressed in relatively mature erythroid progenitors and facilitates the expression of genes associated with differentiation, including the GATA1 gene itself; however, GATA1 represses the expression of GATA2. Switching the GATA factors from GATA2 to GATA1 appears to be one of the key regulatory mechanisms underlying erythroid differentiation. Loss-of-function analyses using mice in vivo have indicated that GATA2 and GATA1 are functionally nonredundant and that neither can compensate for the absence of the other. However, transgenic expression of GATA2 under the transcriptional regulation of the Gata1 gene rescues lethal dyserythropoiesis in GATA1-deficient mice, illustrating that the dynamic expression profiles of these GATA factors are critically important for the maintenance of hematopoietic homeostasis. Analysis of naturally occurring leukemias in GATA1-knockdown mice revealed that leukemic stem cells undergo functional alterations in response to exposure to chemotherapeutic agents. This mechanism may also underlie the aggravating features of relapsing leukemias. Recent hematologic analyses have suggested that disturbances in the balance of the GATA factors are associated with specific types of hematopoietic disorders. Here, we describe GATA1- and GATA2-related hematologic diseases, focusing on the regulation of GATA factor gene expression.
authors.affiliation: Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: rshimizu@med.tohoku.ac.jp.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Shimizu
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D050980:GATA Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D014644:Genetic Variation; D057895:Haploinsufficiency; D006402:Hematologic Diseases / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D054730:Protein Interaction Domains and Motifs; D015533:Transcriptional Activation
chemical_list: D050980:GATA Transcription Factors; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor