Transcriptional regulation mediated by H2A.Z via ANP32e-dependent inhibition of protein phosphatase 2A

Biochim Biophys Acta Gene Regul Mech. 2018 May;1861(5):481-496. doi: 10.1016/j.bbagrm.2018.03.002. Epub 2018 Mar 8.


The mechanisms that regulate H2A.Z and its requirement for transcription in differentiated mammalian cells remains ambiguous. In this study, we identified the interaction between the C-terminus of ANP32e and N-terminus of H2A.Z in a yeast two-hybrid screen. Knockdown of ANP32e resulted in proteasomal degradation and nuclear depletion of H2A.Z or of a chimeric green florescence protein fused to its N-terminus. This effect was reversed by inhibition of protein phosphatase 2A (PP2A) and, conversely, reproduced by overexpression of its catalytic subunit. Accordingly, knockdown of ANP32e inhibited phosphorylation of H2A.Z, whereas a mutation of serine-9 proved its requirement for both the protein's stability and nuclear localization, as did knockdown of the nuclear mitogen and stress-induced kinase 1. Moreover, ANP32e's knockdown also revealed its differential requirement for cell signaling and gene expression, whereas, genome-wide binding analysis confirmed its co-localization with H2A.Z at transcription start sites, as well as, gene bodies of inducible and tissue-specific genes. The data also suggest that H2A.Z restricts transcription, which is moderated by ANP32e at the promoter and gene bodies of expressed genes. Thus, ANP32e, through inhibition of PP2A, is required for nucleosomal inclusion of H2A.Z and the regulation of gene expression.

Keywords: Chromatin immunoprecipitation; Histone; MSK1; Yeast two-hybrid.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence / genetics
  • Cell Nucleus / genetics
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Histones / genetics*
  • Humans
  • Molecular Chaperones
  • Nerve Tissue Proteins / genetics*
  • Nucleosomes / genetics
  • Promoter Regions, Genetic
  • Protein Phosphatase 2 / antagonists & inhibitors
  • Protein Phosphatase 2 / genetics*
  • Saccharomyces cerevisiae / genetics
  • Transcription Initiation Site
  • Transcription, Genetic*


  • Anp32e protein, mouse
  • H2az1 protein, mouse
  • Histones
  • Molecular Chaperones
  • Nerve Tissue Proteins
  • Nucleosomes
  • Protein Phosphatase 2