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Series GSE68618 Query DataSets for GSE68618
Status Public on Sep 01, 2015
Title Aging-dependent demethylation of regulatory elements correlates with chromatin state and improved insulin secretion by pancreatic β cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary Aging at the cellular level is driven by changes in gene activity and epigenetic state that are only partially understood. We performed a comprehensive epigenomic analysis of the pancreatic β cell, key player in glucose homeostasis and diabetes, in adolescent and very old mice. Globally, we observe a general methylation drift resulting in an overall more leveled methylome, suggesting that the maintenance of highly differential methylation patterns becomes compromised with advanced age. Importantly, we discover targeted changes in the methylation status of β cell proliferation and function genes that go against the global methylation drift, are specific to β cells, and correlate with repression of the proliferation program and activation of metabolic regulators. These targeted alterations frequently occur at distal cis-regulator elements, and are associated with specific chromatin marks and transcription factor occupancy in young β cells. Strikingly, we find the insulin secretory response to glucose much improved in mature β cells in mice, as predicted by the changes in methylome and transcriptome and in contrast to the decline in function observed in aged human β cells. Thus, aging of terminally differentiated cells in mammals is not always coupled to functional decline.
 
Overall design RNA-seq was done on 3 biological replicas from old and three from young beta cells. each sample originated from a pool of 5-10 mic.e H3K27me3 ChIP-seq was done with two replicas for old mice (pool of 4-7 mice) and the rest of the ChIPseq (H3K4me1, H3K27ac and young H3K27me3) was sone with one sample (pool of few mice). BIS-seq was done on one sample from a pool of 10 young mice and one sample of a pool of old mice (18-22 months old)
 
Contributor(s) Avrahami D, Li C, Zhang J, Schug J, Avrahami R, Rao S, Stadler M, Burger L, Schübeler D, Glaser B, Kaestner KH
Citation(s) 26321660
Submission date May 06, 2015
Last update date May 15, 2019
Contact name Dana Avrahami Tzfati
E-mail(s) dana.tzfati@mail.huji.ac.il
Organization name Hadassah Hebrew University School of medicine
Department Developmental Biology and cancer research
Lab Dor and Glaser
Street address Ein-Kerem
City Jerusalem
ZIP/Postal code 91120
Country Israel
 
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (16)
GSM1677151 OldBeta_Rep1_RNASeq
GSM1677152 OldBeta_Rep2_RNASeq
GSM1677153 OldBeta_Rep3_RNASeq
Relations
BioProject PRJNA284579
SRA SRP058569

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
GSE68618_RAW.tar 283.6 Mb (http)(custom) TAR (of TAB, TXT)
GSE68618_RawReadCounts.txt.gz 409.3 Kb (ftp)(http) TXT
GSE68618_TrancriptFPKMCounts.txt.gz 854.2 Kb (ftp)(http) TXT
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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