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ZNF 384‐fusion proteins have high affinity for the transcriptional coactivator EP 300 and aberrant transcriptional activities
Author(s) -
Yamamoto Hideyuki,
Hayakawa Fumihiko,
Yasuda Takahiko,
Odaira Koya,
Minamikawa Yuka,
Tange Naoyuki,
Hirano Daiki,
Kojima Yuki,
Morishita Takanobu,
Tsuzuki Shinobu,
Naoe Tomoki,
Kiyoi Hitoshi
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13506
Subject(s) - fusion protein , zinc finger , fusion gene , microbiology and biotechnology , gene , enhancer , transcriptional regulation , biology , chemistry , gene expression , genetics , transcription factor , recombinant dna
Zinc‐finger protein 384 ( ZNF 384) 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 SALL 4 and ID 2 as potential Z‐fusion‐specific transcriptional targets that might lead to the differentiation disorder of Z‐fusion‐positive ALL . The introduction of EP 300‐ ZNF 384 and SYNRG ‐ ZNF 384 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 EP 300 than Wild‐Z. Coexpression of EP 300 specifically enhanced the transcriptional activities of Z‐fusion proteins. We propose the increased EP 300 binding of Z‐fusion proteins as a mechanism for their increased transcriptional activities.