ANP32A regulates histone H3 acetylation and promotes leukemogenesis

Leukemia. 2018 Jul;32(7):1587-1597. doi: 10.1038/s41375-018-0010-7. Epub 2018 Feb 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Apolipoprotein C-I / metabolism
  • Apoptosis
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism*
  • Gene Expression Regulation, Leukemic
  • Gene Knockdown Techniques
  • Histones / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Lipid Metabolism / genetics
  • Mice
  • Nuclear Proteins
  • RNA, Messenger / genetics
  • RNA-Binding Proteins
  • Tumor Stem Cell Assay

Substances

  • ANP32A protein, human
  • APOC1 protein, human
  • Apolipoprotein C-I
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA-Binding Proteins