1. PML4 facilitates erythroid differentiation by enhancing the transcriptional activity of GATA-1.
- Author
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Wu J, Zhou LQ, Yu W, Zhao ZG, Xie XM, Wang WT, Xiong J, Li M, Xue Z, Wang X, Zhang P, Mao BB, Hao DL, Lv X, and Liu DP
- Subjects
- Acetylation, E1A-Associated p300 Protein metabolism, GATA1 Transcription Factor chemistry, GATA1 Transcription Factor metabolism, Gene Expression, Humans, K562 Cells, Nuclear Proteins chemistry, Nuclear Proteins genetics, Promyelocytic Leukemia Protein, Protein Binding, Protein Interaction Domains and Motifs, Protein Isoforms, Trans-Activators genetics, Trans-Activators metabolism, Transcription Factors chemistry, Transcription Factors genetics, Transcription, Genetic, Tumor Suppressor Proteins chemistry, Tumor Suppressor Proteins genetics, Zinc Fingers, Cell Differentiation physiology, Erythroid Cells cytology, Erythroid Cells metabolism, GATA1 Transcription Factor genetics, Nuclear Proteins metabolism, Transcription Factors metabolism, Transcriptional Activation, Tumor Suppressor Proteins metabolism
- Abstract
Promyelocytic leukemia protein (PML) has been implicated as a participant in multiple cellular processes including senescence, apoptosis, proliferation, and differentiation. Studies of PML function in hematopoietic differentiation previously focused principally on its myeloid activities and also indicated that PML is involved in erythroid colony formation. However, the exact role that PML plays in erythropoiesis is essentially unknown. In this report, we found that PML4, a specific PML isoform expressed in erythroid cells, promotes endogenous erythroid genes expression in K562 and primary human erythroid cells. We show that the PML4 effect is GATA binding protein 1 (GATA-1) dependent using GATA-1 knockout/rescued G1E/G1E-ER4 cells. PML4, but not other detected PML isoforms, directly interacts with GATA-1 and can recruit it into PML nuclear bodies. Furthermore, PML4 facilitates GATA-1 trans-activation activity in an interaction-dependent manner. Finally, we present evidence that PML4 enhances GATA-1 occupancy within the globin gene cluster and stimulates cooperation between GATA-1 and its coactivator p300. These results demonstrate that PML4 is an important regulator of GATA-1 and participates in erythroid differention by enhancing GATA-1 trans-activation activity.
- Published
- 2014
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