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

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.

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  • Authors+Show Affiliations

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    Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Japan.

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    Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Japan. Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Japan.

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    Clinical Research Center, Nagoya Medical Center, National Hospital Organization, Nagoya, Japan.

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    Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Japan.

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    Department of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.

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    Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Japan.

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    Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Japan.

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    Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Japan.

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    Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Japan.

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    Department of Biochemistry, School of Medicine, Aichi Medical University, Japan.

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    Nagoya Medical Center, National Hospital Organization, Nagoya, Japan.

    Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Japan.

    Source

    FEBS letters : 2019 Jun 24 pg

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31234226

    Citation

    Yamamoto, Hideyuki, et al. "ZNF384-fusion Proteins Have High Affinity for the Transcriptional Coactivator EP300 and Aberrant Transcriptional Activities." FEBS Letters, 2019.
    Yamamoto H, Hayakawa F, Yasuda T, et al. ZNF384-fusion proteins have high affinity for the transcriptional coactivator EP300 and aberrant transcriptional activities. FEBS Lett. 2019.
    Yamamoto, H., Hayakawa, F., Yasuda, T., Odaira, K., Minamikawa, Y., Tange, N., ... Kiyoi, H. (2019). ZNF384-fusion proteins have high affinity for the transcriptional coactivator EP300 and aberrant transcriptional activities. FEBS Letters, doi:10.1002/1873-3468.13506.
    Yamamoto H, et al. ZNF384-fusion Proteins Have High Affinity for the Transcriptional Coactivator EP300 and Aberrant Transcriptional Activities. FEBS Lett. 2019 Jun 24; PubMed PMID: 31234226.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - ZNF384-fusion proteins have high affinity for the transcriptional coactivator EP300 and aberrant transcriptional activities. AU - Yamamoto,Hideyuki, AU - Hayakawa,Fumihiko, AU - Yasuda,Takahiko, AU - Odaira,Koya, AU - Minamikawa,Yuka, AU - Tange,Naoyuki, AU - Hirano,Daiki, AU - Kojima,Yuki, AU - Morishita,Takanobu, AU - Tsuzuki,Shinobu, AU - Naoe,Tomoki, AU - Kiyoi,Hitoshi, Y1 - 2019/06/24/ PY - 2019/03/01/received PY - 2019/06/12/revised PY - 2019/06/14/accepted PY - 2019/6/25/pubmed PY - 2019/6/25/medline PY - 2019/6/25/entrez KW - SYNRG KW - EP300 KW - ID2 KW - SALL4 KW - ZNF384 fusion proteins JF - FEBS letters JO - FEBS Lett. N2 - 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. SN - 1873-3468 UR - https://www.unboundmedicine.com/medline/citation/31234226/ZNF384-fusion_proteins_have_high_affinity_for_the_transcriptional_coactivator_EP300_and_aberrant_transcriptional_activities L2 - https://doi.org/10.1002/1873-3468.13506 DB - PRIME DP - Unbound Medicine ER -