ZNF384-fusion proteins have high affinity for the transcriptional coactivator EP300 and aberrant transcriptional activities

FEBS Letters

article

Hideyuki Yamamoto¹  Fumihiko Hayakawa¹  Takahiko Yasuda³  Koya Odaira²  Yuka Minamikawa⁴  Naoyuki Tange¹  Daiki Hirano¹  Yuki Kojima¹  Takanobu Morishita¹  Shinobu Tsuzuki⁵  Tomoki Naoe³  Hitoshi Kiyoi¹ 

[1] Department of Hematology and Oncology, Nagoya University Graduate School of Medicine;Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine;Clinical Research Center, Nagoya Medical Center, National Hospital Organization;Department of Analytical Neurobiology, Faculty of Pharmacy, Meijo University;Department of Biochemistry, School of Medicine, Aichi Medical University

关键词: EP300;    ID2;    SALL4;    SYNRG;    ZNF384 fusion proteins;   

DOI  :  10.1002/1873-3468.13506

来源: John Wiley & Sons Ltd.

【 摘 要 】

Zinc-finger protein 384 (ZNF384) fusion (Z-fusion) genes have recently been identified as recurrent fusion genes in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) and have been detected in 7–17% of Philadelphia chromosome-negative BCP-ALL cases. We selected SALL4 and ID2 as potential Z-fusion-specific transcriptional targets that might lead to the differentiation disorder of Z-fusion-positive ALL. The introduction of EP300- ZNF384 and SYNRG-ZNF384 induced the expression of these genes. Z-fusion proteins exhibited stronger transcriptional activities on the promoter or enhancer region of these genes than Wild-Z. Furthermore, GST pull-down assay revealed that Z-fusion proteins associated more strongly with EP300 than Wild-Z. Coexpression of EP300 specifically enhanced the transcriptional activities of Z-fusion proteins. We propose the increased EP300 binding of Z-fusion proteins as a mechanism for their increased transcriptional activities.

【 授权许可】

Unknown