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Series GSE47501 Query DataSets for GSE47501
Status Public on May 31, 2013
Title ATM mediates pRB function to control DNMT1 protein stability and DNA methylation
Organism Mus musculus
Experiment type Expression profiling by array
Summary The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression owing to its ability to physically bind to many of chromatin modifiers. However, the biological and clinical significance of this activity was not well elucidated. To address this, we performed genetic and epigenetic analyses in an Rb-deficient mouse thyroid C cell tumor model. Here we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability, and hence controls the DNA methylation status in the promoter of at least Ink4a, Shc2, FoxO6 and Noggin genes. Further, we demonstrate that inactivation of pRB promotes the Tip60 (acetyltransferase)-dependent ATM activation, allows activated ATM to physically bind to DNMT1 forming a complex with Tip60 and UHRF1 (E3 ligase), and consequently accelerates DNMT1 ubiquitination driven by Tip60-dependent acetylation. Our results indicate that inactivation of pRB pathway in coordination with aberration in DNA damage response leads to abnormal DNA methylation pattern by affecting the stability of DNMT1.
Overall design 163; Rb-/-;ATM-/- MEFs, D4; DNMT1 knockdown from 163 cells and analysed at day 4, WT8S; 163 cells reconstituted with ATM expression vector
Contributor(s) Shamma A, Nishiuchi T, Takahashi C
Citation(s) 23754744
Submission date May 30, 2013
Last update date Jan 19, 2018
Contact name Awad Shamma
Phone +81-76-264-6751
Fax +81-76-234-4521
Organization name Kanazawa Uiniversity
Department Cancer Research Institute
Lab Division of Oncology and Molecular Biology
Street address Kakuma-machi
City Kanazawa
State/province Ishikawa
ZIP/Postal code 920-1192
Country Japan
Platforms (1)
GPL10333 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Feature Number version)
Samples (3)
GSM1151216 163
GSM1151217 D4
GSM1151218 WT8S
BioProject PRJNA205897

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE47501_RAW.tar 13.1 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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