| 2014 |
ANP32E is a histone chaperone that specifically removes H2A.Z from chromatin. It is a member of the p400/TIP60 H2A.Z histone-exchange complex and interacts with a short region of the docking domain of H2A.Z through a novel motif called the H2A.Z interacting domain (ZID). Crystal structure at 1.48 Å of the ANP32E-ZID/H2A.Z/H2B complex reveals that ANP32E stabilizes the H2A.Z/H2B dimer through a specific extension of the H2A.Z C-terminal α-helix. In ANP32E-knockout cells, H2A.Z shows genome-wide enrichment and accumulation at enhancers and insulators. |
Crystal structure (1.48 Å), Co-IP, co-fractionation, biochemical pulldown, chromatin immunoprecipitation followed by sequencing (ChIP-seq) in ANP32E-/- cells |
Nature |
High |
24463511
|
| 2014 |
Anp32e preferentially associates with H2A.Z-H2B dimers over canonical H2A-H2B dimers both in vitro and in vivo. Crystal structure of the Anp32e chaperone domain (residues 186–232) bound to H2A.Z-H2B shows that residues 214–224 (absent in other Anp32 family members) specifically contact the extended H2A.Z αC helix. Overexpression of Anp32e causes global H2A.Z loss at +1 nucleosomes; depletion causes moderate global H2A.Z increase at +1 nucleosomes. |
Crystal structure, in vitro binding assays, genome-wide ChIP-seq, gain- and loss-of-function experiments |
Cell Research |
High |
24613878
|
| 2015 |
Anp32e is rapidly recruited to DNA double-strand breaks (DSBs) and removes H2A.Z from nucleosomes, returning H2A.Z levels to basal within 10 min of DNA damage. H2A.Z removal by Anp32e disrupts inhibitory interactions between the histone H4 tail and the nucleosome surface, facilitating H4 acetylation. Loss of Anp32e leads to elevated nucleosomal H2A.Z, hypoacetylated chromatin at DSBs, increased CtIP-dependent end resection, ssDNA accumulation, and increased alternative non-homologous end joining repair. |
Live-cell imaging of DSB-recruited Anp32e, ChIP at DSBs, knockdown/knockout with specific repair pathway readouts, H4 acetylation assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
26034280
|
| 2006 |
Anp32e/Cpd1 co-localizes with protein phosphatase 2A (PP2A) at synapses during cerebellar synaptogenesis. Synaptic Anp32e interacts with and inhibits PP2A activity. Phosphorylation of Anp32e is required for the Anp32e–PP2A interaction. A high-molecular-weight (74/76 kDa) membrane-bound form of Anp32e is expressed in a spatiotemporal pattern correlated with the cerebellar synaptogenesis period. |
Co-immunoprecipitation, PP2A activity assays, subcellular fractionation, electron microscopy, phosphorylation assays, ataxic mutant mouse models |
The European Journal of Neuroscience |
Medium |
16420440
|
| 2018 |
ANP32E interacts with H2A.Z (C-terminus of ANP32E with N-terminus of H2A.Z, identified by yeast two-hybrid). ANP32E knockdown leads to proteasomal degradation and nuclear depletion of H2A.Z; this is reversed by PP2A inhibition and reproduced by PP2A catalytic subunit overexpression. ANP32E knockdown reduces H2A.Z phosphorylation; mutation of H2A.Z serine-9 abrogates its protein stability and nuclear localization. Nuclear mitogen and stress-induced kinase 1 (MSK1) knockdown phenocopies this effect. |
Yeast two-hybrid, knockdown, GFP-H2A.Z chimera, PP2A inhibitor treatment, site-directed mutagenesis (S9A), genome-wide ChIP-seq |
Biochimica et Biophysica Acta: Gene Regulatory Mechanisms |
Medium |
29524612
|
| 2020 |
ANP32E antagonizes H2A.Z accumulation genome-wide to restrict chromatin accessibility in mouse fibroblasts. In the absence of ANP32E, H2A.Z accumulates at promoters in a hierarchical manner (first downstream, then upstream of the TSS), coinciding with improved nucleosome positioning, increased transcription factor binding, and elevated neighboring gene expression. |
ATAC-seq, ChIP-seq, ANP32E knockout mouse fibroblasts, MNase-seq, RNA-seq |
Nature Communications |
High |
33033242
|
| 2021 |
In post-mitotic neurons, Anp32e regulates H2A.Z binding under steady-state conditions. Anp32e depletion causes H2A.Z-dependent impairment in transcription and dendritic arborization in cultured hippocampal neurons. In vivo, Anp32e depletion impairs recall of contextual fear memory and transcriptional regulation. Anp32e has lesser impact on stimulus-induced (activity-dependent) H2A.Z removal compared to steady-state regulation. |
Conditional knockdown in hippocampal neurons, ChIP-seq, RNA-seq, fear-conditioning behavioral assay, dendritic morphology analysis |
Cell Reports |
High |
34407406
|
| 2022 |
In zebrafish, Anp32e restricts H2A.Z accumulation specifically at Sox motif-containing promoters. Genetic removal of Anp32e leads to precocious H2A.Z accumulation and premature transcriptional activation of Sox motif-associated developmental genes before gastrulation. |
Genetic knockout of anp32e in zebrafish, ChIP-seq, RNA-seq |
Developmental Biology |
High |
38159623 38187710
|
| 2022 |
Anp32e promotes renal interstitial fibrosis by upregulating TGF-β1 and p-Smad3, leading to deposition of fibronectin and collagen type I. Overexpression of Anp32e alone (without TGF-β1 stimulation) induces fibrosis-related protein deposition; this is reversed by the TGF-β1 inhibitor SB431542, placing Anp32e upstream of the TGF-β1/Smad3 pathway. |
Gain- and loss-of-function in BUMPT cells and UUO mouse model, western blot, TGF-β1 inhibitor rescue assay |
International Journal of Biological Sciences |
Medium |
36263179
|
| 2024 |
ANP32E preferentially interacts with H2A.Z during the G1 phase of the cell cycle in both cytoplasm and nucleoplasm of human U2OS cells. Most ANP32E is cytoplasmic, not chromatin-associated, and is not a stable component of the p400 remodeling complex. In the cytoplasm, ANP32E interacts with H2A.Z in G1 in response to increased H2A.Z protein abundance and regulates H2A.Z protein stability. This challenges the model that ANP32E removes H2A.Z from chromatin as part of a remodeling complex. |
Cell cycle synchronization, Co-IP, subcellular fractionation, mass spectrometry, U2OS cell knockdown with growth assays |
Molecular and Cellular Biology |
Medium |
38482865
|
| 2025 |
ANP32E-driven H2A.Z turnover alters RNA polymerase II processivity, leading to accumulation of long R-loops at transcription-replication conflict (TRC) sites. ANP32E overexpression enhances TRC formation and activates ATR-dependent DNA damage response, predisposing cancer cells to R-loop-mediated genomic fragility. Tumors with co-upregulation of MYC and ANP32E show increased genomic instability. |
Genome-wide R-loop mapping (DRIP-seq), RNA Pol II ChIP-seq, ATR inhibitor sensitivity assays, ANP32E overexpression in breast cancer cells, patient genomic data analysis |
Nature Communications |
Medium |
40382323
|
| 2026 |
ANP32E and the SRCAP subunit VPS72 co-occupy active gene promoters and function antagonistically on H2A.Z. VPS72 promotes H2A.Z incorporation, acetylation, BRG1 recruitment, and transcription; ANP32E constrains these features by stabilizing nucleosomes. Loss of ANP32E increases VPS72 binding, chromatin accessibility, and transcription; co-depletion of VPS72 reverses these effects. In vitro reconstitution assays demonstrate that ANP32E promotes nucleosome assembly and prevents DNA unwrapping. |
ChIP-seq, ATAC-seq, RNA-seq, genetic co-depletion epistasis, in vitro nucleosome reconstitution assays |
Research Square (preprint)preprint |
Medium |
41646306
|
| 2018 |
ANP32E promotes G1/S cell cycle transition in triple-negative breast cancer cells by transcriptionally inducing E2F1. ANP32E inhibition suppresses tumor formation in vivo. |
siRNA knockdown, overexpression, cell cycle analysis, E2F1/cyclin E expression analysis, xenograft mouse model |
Molecular Oncology |
Low |
29633513
|
| 2024 |
ANP32E regulates esophageal cancer progression and ferroptosis via the p53/SLC7A11 axis. ANP32E depletion increases p53 expression; p53 inhibition partially reverses the suppressed proliferation and enhanced ferroptosis in ANP32E-depleted cells. |
ANP32E knockout cell models, xenograft, RNA-seq, ferroptosis inhibitor rescue (ferrostatin-1), p53 inhibitor rescue, western blot |
International Immunopharmacology |
Low |
39566382
|