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GEO help: Mouse over screen elements for information. |
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Status |
Public on May 22, 2018 |
Title |
Transcriptional regulation mediated by H2A.Z via ANP32e-dependent inhibition of protein phosphatase 2A |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
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 genes. The data also suggest that H2A.Z restricts transcription, which is moderated by ANP32e after induction of transcriptional activity of inducible and housekeeping genes vs. constitutively-expressed tissue-specific genes during cellular growth. Thus, ANP32e, through inhibition of PP2A, is required for nucleosomal inclusion of H2A.Z and the regulation of gene expression.
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Overall design |
Methods: Hearts were extracted from from mice subjecetd to Transaortic coarctation or sham operations. The hearts were sent to Active Motif for H2Az- or Anp32e-ChIP-Seq.
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Contributor(s) |
Abdellatif M, Sayed D |
Citation(s) |
29524612 |
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Submission date |
Oct 06, 2017 |
Last update date |
Jul 25, 2021 |
Contact name |
Danish Sayed |
E-mail(s) |
sayeddh@njms.rutgers.edu
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Phone |
(973) 972-5243
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Organization name |
Rutgers-NJMS
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Department |
CBMM
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Lab |
MSB G 626
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Street address |
185 south orange avenue
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City |
Newark |
State/province |
NJ |
ZIP/Postal code |
07103 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (5)
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Relations |
BioProject |
PRJNA413542 |
SRA |
SRP119534 |
Supplementary file |
Size |
Download |
File type/resource |
GSE104702_0030UMDNJ_ANP32E_mm10_actregs.xlsx.gz |
1.2 Mb |
(ftp)(http) |
XLSX |
GSE104702_2666Rutgers_H2AZ_actregs.xlsx.gz |
4.2 Mb |
(ftp)(http) |
XLSX |
GSE104702_RAW.tar |
572.9 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
Processed data are available on Series record |
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