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Series GSE57353 Query DataSets for GSE57353
Status Public on Jul 17, 2015
Title Genome-wide DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi-Goutières syndrome
Organism Homo sapiens
Experiment type Other
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary Aicardi-Goutières syndrome (AGS) is a severe childhood inflammatory disorder that shows clinical and genetic overlap with systemic lupus erythematosus (SLE). AGS is thought to arise from the accumulation of incompletely metabolized endogenous nucleic acid species owing to mutations in nucleic acid degrading enzymes TREX1 (AGS1), RNase H2 (AGS2, 3 and 4) and SAMHD1 (AGS5). However, the identity and source of such immunogenic nucleic acid species remain undefined. Using genome-wide approaches, we show that fibroblasts from AGS patients with AGS1-5 mutations are burdened by excessive loads of RNA:DNA hybrids. Using MethylC-seq, we show that AGS fibroblasts display pronounced and global loss of DNA methylation and demonstrate that AGS-specific RNA:DNA hybrids often occur within DNA hypomethylated regions. Altogether, our data suggest that RNA:DNA hybrids may represent a common immunogenic form of nucleic acids in AGS and provide the first evidence of epigenetic perturbations in AGS, furthering the links between AGS and SLE.
Overall design DNA-RNA immunoprecipitation (DRIP-seq) was performed on control 1, control 3, AGS1 P1, AGS1 P2, AGS2 P1, AGS2 P2, AGS4 P1, AGS4 P2, AGS5 P1 and AGS5 P2. MethylC-seq was performed on control 1, control 2, AGS1 P1, AGS2 P1, AGS4 P1 and AGS5 P1. Reduced representation bisulfite sequencing (RRBS) was performed on GM12697 and AGS2 LCL cell lines. RNA-seq was performed on 2 biological replicates each of control 1, AGS1 P1, AGS2 P1, AGS2 P2, AGS4 P1, AGS4 P2 and AGS5 P1.
Contributor(s) Lim Y, Sanz LA, Xu X, Hartono SR, Chedin F
Citation(s) 26182405
Submission date May 06, 2014
Last update date May 15, 2019
Contact name Yoong Wearn Lim
Organization name University of California, Davis
Department Molecular and Cellular Biology
Lab Chedin
Street address One Shields Avenue
City Davis
State/province CA
ZIP/Postal code 95616
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (33)
GSM1380853 Digested input
GSM1380854 Control 1 DRIP-seq
GSM1380855 AGS1 P1 DRIP-seq
BioProject PRJNA246322
SRA SRP041718

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE57353_AGS1s_drip.bed.gz 258.5 Kb (ftp)(http) BED
GSE57353_AGS2s_drip.bed.gz 273.0 Kb (ftp)(http) BED
GSE57353_AGS4s_drip.bed.gz 253.1 Kb (ftp)(http) BED
GSE57353_AGS5s_drip.bed.gz 247.5 Kb (ftp)(http) BED
GSE57353_RAW.tar 3.3 Gb (http)(custom) TAR (of WIG)
GSE57353_RNAseq_count_table.txt.gz 725.4 Kb (ftp)(http) TXT
GSE57353_controls_drip.bed.gz 185.0 Kb (ftp)(http) BED
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Processed data provided as supplementary file
Processed data are available on Series record
Raw data are available in SRA

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