ZNF384‐fusion proteins have high affinity for the transcriptional coactivator EP300 and aberrant transcriptional activities. Issue 16 (10th July 2019)

• Record Type: Journal Article
• Authors: Yamamoto, Hideyuki; Hayakawa, Fumihiko; Yasuda, Takahiko; Odaira, Koya; Minamikawa, Yuka; Tange, Naoyuki; Hirano, Daiki; Kojima, Yuki; Morishita, Takanobu; Tsuzuki, Shinobu; Naoe, Tomoki; Kiyoi, Hitoshi
• Is Part Of: FEBS letters. Volume 593:Issue 16(2019)
• Page Start: 2151
• Page End: 2161
• Publication Date: 2019-07-10
• Subjects: EP300 -- ID2 -- SALL4 -- SYNRG -- ZNF384 fusion proteins; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13506
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract :