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ANP32A regulates histone H3 acetylation and promotes leukemogenesis

Leukemia volume 32, pages 1587–1597 (2018)Cite this article

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Abstract

Deregulation of key regulators of histone modification is important in the initiation and progression of human leukemia. Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) participates in histone acetylation and its role in acute myeloid leukemia remains unclear. Here we observed significant upregulation of ANP32A in primary AML cells, which was essential for AML cell proliferation, survival, and colony formation. Integrative analysis of the genome-wide histone H3 acetylation and gene expression demonstrated that ANP32A deficiency reduced histone H3 acetylation, in accordance with changes in gene expression. Notably, significant histone H3 acetylation enrichment was associated with mRNA changes in lipid-related genes, including APOC1, PCSK9, P2RX1, and LPPR3. Indeed, over-expression of APOC1 partially compensated the proliferation-defect phenotype in ANP32A deficient AML cells while APOC1 knockdown alone mimicked the effect of ANP32A deficiency. Collectively, our data indicate that ANP32A is a novel regulator of histone H3 acetylation and promotes leukemogenesis.

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Funding

This work was supported by the National Natural Science Foundation of China (31371481 to Z. H., 91731302 to Q.F.W., 81670140 to Z. H., 81425003 to Q.F.W., 81770168 to D. L.), and National Key Basic Research Program of China (2014CB542001 to Q.F.W.), Social Development Project of Jiangsu Province (CXTDA2017014).

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  1. Xuejing Yang, Bin Lu and Xueqin Sun contributed equally to this work

Authors and Affiliations

  1. Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China

    Xuejing Yang & Qian-fei Wang

  2. University of Chinese Academy of Sciences, Beijing, China

    Xuejing Yang & Qian-fei Wang

  3. College of Life Sciences, Key Laboratory of Cell Hemostasis of Hubei Province, Wuhan University, Wuhan, Hubei, China

    Bin Lu, Xueqin Sun, Cuijuan Han, Min Wang & Zan Huang

  4. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Chunling Fu, Puneet Opal, Qiang Wen & John D. Crispino

  5. Blood Diseases Institute, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China

    Chunling Fu & Kailin Xu

  6. Department of Hematology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Dengju Li

  7. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Zhichao Chen

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  1. Xuejing Yang
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Yang, X., Lu, B., Sun, X. et al. ANP32A regulates histone H3 acetylation and promotes leukemogenesis. Leukemia 32, 1587–1597 (2018). https://doi.org/10.1038/s41375-018-0010-7

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