PML4 facilitates erythroid differentiation by enhancing the transcriptional activity of GATA-1

• Published in: Blood 2014-01, Vol.123 (2), p.261-270
• Main Authors: Wu, Jie, Zhou, Li-Quan, Yu, Wei, Zhao, Zhi-Guo, Xie, Xue-Min, Wang, Wen-Tian, Xiong, Jian, Li, Man, Xue, Zheng, Wang, Xing, Zhang, Peng, Mao, Bei-Bei, Hao, De-Long, Lv, Xiang, Liu, De-Pei
• Format: Article
• Language: English
• Subjects: Acetylation; Cell Differentiation - physiology; E1A-Associated p300 Protein - metabolism; Erythroid Cells - cytology; Erythroid Cells - metabolism; GATA1 Transcription Factor - chemistry; GATA1 Transcription Factor - genetics; GATA1 Transcription Factor - metabolism; Gene Expression; Humans; K562 Cells; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; 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 Factors - metabolism; Transcription, Genetic; Transcriptional Activation; Tumor Suppressor Proteins - chemistry; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Zinc Fingers
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-02-483289

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. •PML4 promotes erythroid differentiation in K562, primary erythroid cells, and GATA-1–rescued G1E-ER4 cells, but not in GATA-1–deficient G1E cells.•PML4 interacts with GATA-1 and enhances its transcriptional activity by stimulating GATA-1/P300 cooperation and GATA-1 acetylation.