title: GATA1 Activity Governed by Configurations ofcis-Acting Elements.
abstract: The transcription factor GATA1 regulates the expression of essential erythroid and megakaryocytic differentiation genes through binding to the DNA consensus sequence WGATAR. The GATA1 protein has four functional domains, including two centrally located zinc-finger domains and two transactivation domains at the N- and C-termini. These functional domains play characteristic roles in the elaborate regulation of diversified GATA1 target genes, each of which exhibits a unique expression profile. Three types of GATA1-related hematological malignancies have been reported. One is a structural mutation in the GATA1 gene, resulting in the production of a short form of GATA1 that lacks the N-terminal transactivation domain and is found in Down syndrome-related acute megakaryocytic leukemia. The other two arecis-acting regulatory mutations affecting expression of theGata1gene, which have been shown to cause acute erythroblastic leukemia and myelofibrosis in mice. Therefore, imbalanced gene regulation caused by qualitative and quantitative changes in GATA1 is thought to be involved in specific hematological disease pathogenesis. In the present review, we discuss recent advances in understanding the mechanisms of differential transcriptional regulation by GATA1 during erythroid differentiation, with special reference to the binding kinetics of GATA1 at conformation-specific binding sites.
authors.affiliation: Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hasegawa
authors.affiliation: Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan; Medical Mega-Bank Organization, Tohoku University, Sendai, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Shimizu
keywords: DNA-binding domain; GATA1 transcription factor; cis-acting elements; erythropoiesis; protein–protein interactions