N- and C-terminal transactivation domains of GATA1 protein coordinate hematopoietic program.

The Journal of Biological Chemistry
Hiroshi KanekoR Shimizu

Abstract

Transcription factor GATA1 regulates the expression of a cluster of genes important for hematopoietic cell differentiation toward erythroid and megakaryocytic lineages. Three functional domains have been identified in GATA1, a transactivation domain located in the N terminus (N-TAD) and two zinc finger domains located in the middle of the molecule. Although N-TAD is known as a solitary transactivation domain for GATA1, clinical observations in Down syndrome leukemia suggest that there may be additional transactivation domains. In this study, we found in reporter co-transfection assays that transactivation activity of GATA1 was markedly reduced by deletion of the C-terminal 95 amino acids without significant attenuation of the DNA binding activity or self-association potential. We therefore generated transgenic mouse lines that expressed GATA1 lacking the C-terminal region (GATA1-ΔCT). When we crossed these transgenic mouse lines to the Gata1-deficient mouse, we found that the GATA1-ΔCT transgene rescued Gata1-deficient mice from embryonic lethality. The embryos rescued with an almost similar level of GATA1-ΔCT to endogenous GATA1 developed beyond embryonic 13.5 days, showing severe anemia with accumulation of immature erythroid...Continue Reading

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Citations

Sep 8, 2012·Current Opinion in Hematology·Belinda K SingletonDavid J Anstee
Dec 26, 2013·Molecular Genetics and Genomics : MGG·Yanyan TangChao Qin
Jul 31, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Harumi Y MukaiMasayuki Yamamoto
Oct 15, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Ritsuko ShimizuMasayuki Yamamoto
May 29, 2016·Experimental Hematology·Ritsuko Shimizu, Masayuki Yamamoto
Apr 8, 2017·IUBMB Life·George Papanikolaou, Kostas Pantopoulos
May 25, 2016·Molecular and Cellular Biology·Atsushi HasegawaRitsuko Shimizu
Oct 28, 2019·IUBMB Life·Te Ling, John D Crispino
Sep 4, 2012·Cancer Science·Ritsuko Shimizu, Masayuki Yamamoto
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Jan 26, 2017·Frontiers in Oncology·Atsushi Hasegawa, Ritsuko Shimizu
Feb 22, 2021·Blood Cells, Molecules & Diseases·Maria Carolina Costa Melo SvidnickiSara Teresinha Olalla Saad

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