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Series GSE99607 Query DataSets for GSE99607
Status Public on Jun 11, 2018
Title Impaired DNA demethylation of C/EBP sites causes premature aging
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Expression profiling by array
Summary Changes in DNA methylation are among the best-documented epigenetic alterations accompanying organismal aging. However, whether and how altered DNA methylation is causally involved in aging have remained elusive. GADD45α (growth arrest and DNA damage protein 45A) and ING1 (inhibitor of growth family member 1) are adapter proteins for site-specific demethylation by TET (ten-eleven translocation) methylcytosine dioxygenases. Here we show that Gadd45a/Ing1 double-knockout mice display segmental progeria and phenocopy impaired energy homeostasis and lipodystrophy characteristic of Cebp (CCAAT/enhancer-binding protein) mutants. Correspondingly, GADD45α occupies C/EBPβ/δ-dependent superenhancers and, cooperatively with ING1, promotes local DNA demethylation via long-range chromatin loops to permit C/EBPβ recruitment. The results indicate that enhancer methylation can affect aging and imply that C/EBP proteins play an unexpected role in this process. Our study suggests a causal nexus between DNA demethylation, metabolism, and organismal aging.

This SuperSeries is composed of the SubSeries listed below.
Overall design Refer to individual Series
Citation(s) 29884649
Submission date Jun 02, 2017
Last update date Jul 25, 2021
Contact name Emil Karaulanov
Organization name Institute of Molecular Biology
Lab Bioinformatics Core Facility
Street address Ackermannweg 4
City Mainz
ZIP/Postal code 55128
Country Germany
Platforms (4)
GPL10787 Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (58)
GSM2648459 MEF_ChIPSeq_Co_G45a_rep1
This SuperSeries is composed of the following SubSeries:
GSE99601 Whole genome bisulfite sequencing of Ing1/Gadd45a double knockout and wildtype mouse embryonic fibroblasts
GSE99602 GADD45a ChIP-Seq in mouse embryonic fibroblasts
GSE99603 ING1 ChIP-Seq in mouse embryonic fibroblasts
BioProject PRJNA388882

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE99607_RAW.tar 1.7 Gb (http)(custom) TAR (of BW, TAR, TSV, TXT)
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