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Series GSE153331 Query DataSets for GSE153331
Status Public on Jan 10, 2024
Title Astrocyte Reactivity and Cognitive Decline Follow Chronic Heterochromatin Loss in Neurons
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 In aging cells and animal models of premature aging, heterochromatin loss coincides with transcriptional disruption including the activation of normally silenced endogenous retroviruses (ERVs). Here we show that loss of heterochromatin maintenance and de-repression of ERVs results in a chronic inflammatory environment characterized by neurodegeneration and cognitive decline. We discovered differential contributions of HP1 proteins to ERV silencing where HP1γ is necessary and sufficient for H4K20me3 deposition and HP1β deficiency is detrimental to DNA maintenance methylation. Progressive ERV de-repression in HP1β/γ DKO mice was followed by stimulation of the integrated stress response, an increase of Complement 3+ reactive astrocytes and phagocytic microglia. This chronic inflammatory state coincided with age-dependent reductions in dendrite complexity and cognition. Our results demonstrate the importance of preventing loss of epigenetic maintenance, as this will be the only way postmitotic neuronal genomes can be protected and/or renewed.
Overall design RNAseq in mouse young and aged hippocampus, RRBS and ChIPseq in mouse ESCs, RRBS in Hippocampal lysates
Web link
Contributor(s) Newman AG, Sharif J, Bessa P, Zaqout S, Brown J, Richter D, Dannenberg R, Nakayama M, Mueller S, Schaub T, Manickaraj S, Böhm-Sturm P, Ohara O, Koseki H, Singh PB, Tarabykin V
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Submission date Jun 26, 2020
Last update date Jun 05, 2024
Contact name Andrew Newman
Organization name Charité Universitätsmedizin Berlin
Department Institute for Cell and Neurobiology
Lab Andrew Newman
Street address Charitéplatz 1
City Berlin
ZIP/Postal code 10117
Country Germany
Platforms (3)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (71)
GSM4640634 WT young hippocampus rep1
GSM4640635 WT young hippocampus rep2
GSM4640636 WT young hippocampus rep3
BioProject PRJNA642104
SRA SRP268999

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE153331_Annotated.DMRs.meth.diff.methperc.csv.gz 72.1 Mb (ftp)(http) CSV
GSE153331_RAW.tar 2.4 Gb (http)(custom) TAR (of BEDGRAPH, BW, COV)
GSE153331_colData.txt.gz 248 b (ftp)(http) TXT
GSE153331_counts_all.txt.gz 919.3 Kb (ftp)(http) TXT
GSE153331_methylkit_output_combined_contrasts.rds.gz 1.6 Gb (ftp)(http) RDS
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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