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Series GSE131336 Query DataSets for GSE131336
Status Public on Sep 10, 2019
Title Chromatin architecture as a checkpoint for NASH-associated liver injury
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Nonalcoholic steatohepatitis (NASH) is a progressive liver disease that is characterized by liver injury, inflammation and fibrosis. NASH pathogenesis is linked to reprogramming of chromatin landscape in the liver that predisposes hepatocytes to stress-induced tissue injury. However, the molecular nature of the putative checkpoint that maintains chromatin architecture and preserves hepatocyte health remains elusive. Here we show that heterogeneous nuclear ribonucleoprotein U (hnRNPU), a nuclear matrix protein that governs chromatin architecture and gene transcription, is a critical factor that couples chromatin disruption to NASH pathogenesis. RNA-seq and ChIP-seq studies revealed an extensive overlap between hnRNPU occupancy and altered gene expression during NASH. Hepatocyte-specific inactivation of hnRNPU disrupted liver chromatin accessibility, activated the molecular signature of NASH and sensitized mice to diet-induced NASH pathogenesis. Mechanistically, hnRNPU deficiency stimulated the expression of a truncated isoform of TrkB that promotes inflammatory signaling in hepatocytes and stress-induced cell death. These findings illustrate a novel mechanism through which disruptions of chromatin architecture drive the emergence of disease-specific signaling patterns that promote liver injury and exacerbate NASH pathogenesis.
Overall design 6 biological replicates were analyzied in each group for ATAC-seq (control vs liver specific knockout); 2 control and 3 liver specific knockout samples were used in RNA-seq
Contributor(s) Liu T, Xiong J, Lin J
Citation(s) 31469911
Submission date May 16, 2019
Last update date Sep 10, 2019
Contact name Jiandie Lin
Phone 7346153512
Organization name University of Michigan
Department Cell & Developmental Biology, Life Science Institute
Lab Jiandie Lin Lab
Street address 210 Washtenaw Ave
City Ann Arbor
State/province MI
ZIP/Postal code 48103
Country USA
Platforms (2)
GPL23479 BGISEQ-500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (17)
GSM3770620 mouse liver ATAC-seq Ctrl1
GSM3770621 mouse liver ATAC-seq Ctrl2
GSM3770622 mouse liver ATAC-seq Ctrl3
BioProject PRJNA543292
SRA SRP198634

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Supplementary file Size Download File type/resource
GSE131336_DESeq2_hnrnpu_ATAC_seq.csv.gz 12.5 Mb (ftp)(http) CSV
GSE131336_DESeq2_hnrnpu_RNA_seq.csv.gz 659.2 Kb (ftp)(http) CSV
GSE131336_RAW.tar 4.9 Gb (http)(custom) TAR (of BW)
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Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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