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Series GSE104702 Query DataSets for GSE104702
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
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.
 
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.
 
Contributor(s) Abdellatif M, Sayed D
Citation(s) 29524612
Submission date Oct 06, 2017
Last update date Jul 25, 2021
Contact name Danish Sayed
E-mail(s) sayeddh@njms.rutgers.edu
Phone (973) 972-5243
Organization name Rutgers-NJMS
Department CBMM
Lab MSB G 626
Street address 185 south orange avenue
City Newark
State/province NJ
ZIP/Postal code 07103
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (5)
GSM2806123 H2Az_ChIP-Seq Sham
GSM2806124 H2Az_ChIP-Seq TAC
GSM2806125 ANP32e_ChIP_Seq Sham
Relations
BioProject PRJNA413542
SRA SRP119534

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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 SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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