title: PML4 facilitates erythroid differentiation by enhancing the transcriptional activity of GATA-1.
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.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, and.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Li-Quan
authors.initials: LQ
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Zhao
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Xie
authors.forename: Wen-Tian
authors.initials: WT
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Xiong
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xue
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Mao
authors.forename: De-Long
authors.initials: DL
authors.lastname: Hao
authors.forename: Xiang
authors.initials: X
authors.lastname: Lv
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
mesh_terms: D000107:Acetylation; D002454:Cell Differentiation / Q000502:physiology*; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D020014:K562 Cells; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D050982:GATA1 Transcription Factor; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D050881:E1A-Associated p300 Protein