PU.1 is one of the proteins that interacts with the GATA-1 DNA binding domain and there is reciprocal inhibition between the two proteins. The PU.1 transactivation (TAD) and DNA binding domains are reported to be involved in the interaction and we have noted that the PU.1 TAD shares structural homology with the TAD of p53. In collaboration with the laboratory of Jim Omichinski we have shown that the p53 TAD also interacts in vitro and in vivo with the GATA-1 DNA binding domain. The linker and C-finger of GATA-1 are required for the interaction. The proteins reciprocally inhibit the transactivation activity of one another in an erythroid precursor cell line, 6C2. GATA-1 may be required to prevent p53 induction during the nuclear condensation and enucleation that precedes erythrocyte formation or during the polyploidization of megakaryocytes. In collaboration with Masi Yamamoto we are testing mutants of GATA-1 that do not interact with p53 in rescue assays in GATA1.05 cells and mice to determine the role of this interaction during hematopoiesis.
| Planutis, Antanas; Xue, Li; Trainor, Cecelia D et al. (2017) Neomorphic effects of the neonatal anemia (Nan-Eklf) mutation contribute to deficits throughout development. Development 144:430-440 |
| Hasegawa, Atsushi; Kaneko, Hiroshi; Ishihara, Daishi et al. (2016) GATA1 Binding Kinetics on Conformation-Specific Binding Sites Elicit Differential Transcriptional Regulation. Mol Cell Biol 36:2151-67 |
| Zhu, Jianqiong; Chin, Kyung; Aerbajinai, Wulin et al. (2011) Recombinant erythroid Kruppel-like factor fused to GATA1 up-regulates delta- and gamma-globin expression in erythroid cells. Blood 117:3045-52 |
| Giles, K E; Gowher, H; Ghirlando, R et al. (2010) Chromatin boundaries, insulators, and long-range interactions in the nucleus. Cold Spring Harb Symp Quant Biol 75:79-85 |
| Trainor, Cecelia D; Mas, Caroline; Archambault, Patrick et al. (2009) GATA-1 associates with and inhibits p53. Blood 114:165-73 |
