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Series GSE46103 Query DataSets for GSE46103
Status Public on Oct 19, 2013
Title WIP1 controls global heterochromatin silencing via ATM/BRCA1-dependent DNA methylation
Organism Mus musculus
Experiment type Expression profiling by array
Summary WIP1 phosphatase is emerging as an important regulator of tumorigenesis, but no unifying mechanistic network has been proposed. Here we found that WIP1 plays a key role in the transcriptional regulation of heterochromatin-associated DNA sequences in germ-line and cancer cells. WIP1 was required for epigenetic remodeling of repetitive DNA elements within the heterochromatin, including L1 LINE retrotransposons. Mechanistically, WIP1regulated an ATM-dependent increase in BRCA1 occupancy on L1 LINEs, resulting in closed chromatin without ubiquitination of histone H2A. This mechanism appeared to be dependent on the ability of BRCA1 to bind the heterochromatin protein HP1, the recruitment of DNA methyltransferases, and subsequent DNA methylation. Attenuation of ATM, in turn, reversed heterochromatin methylation in both germ-line and cancer cells. DNA methylation plays a central role in the generation of mutations in human tumors and we found that WIP1 levels strongly correlated with C-to-T substitutions and a total mutation load in primary breast cancers. We propose that WIP1 plays an important role in the regulation of DNA methylation and global heterochromatin silencing, and thus is critical in maintaining genome integrity during development and in cancer.
 
Overall design Total RNA was extracted from control spermatids, Wip1-/- and Wip1-/- Atm+/- spermatids. The final cRNA samples were hybridized in triplicates to Illumina Mouse WG-6 v2.0 Expression arrays.
 
Contributor(s) Filipponi D, Müller J, Bulavin D
Citation(s) 24135283
Submission date Apr 16, 2013
Last update date Jan 16, 2019
Contact name Julius Müller
Organization name A*Star Singapore
Department IMCB
Lab Ernesto Guccione
Street address 61 Biopolis Drive
City Singapore
ZIP/Postal code 138673
Country Singapore
 
Platforms (1)
GPL6887 Illumina MouseWG-6 v2.0 expression beadchip
Samples (9)
GSM1123717 ST_WT−1
GSM1123718 ST_WT−2
GSM1123719 ST_WT−3
Relations
BioProject PRJNA197260

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
GSE46103_RAW.tar 15.8 Mb (http)(custom) TAR
GSE46103_non-normalized.txt.gz 1.6 Mb (ftp)(http) TXT
Processed data included within Sample table

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