Transcriptomics

Dataset Information

0

Chromatin architecture as a checkpoint for NASH-associated liver injury


ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE131336 | GEO | 2019/09/10

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2022-07-08 | PXD026717 | Pride
2022-07-13 | GSE173735 | GEO
2022-07-13 | GSE173734 | GEO
2024-04-26 | GSE230700 | GEO
| PRJNA543292 | ENA
2013-04-02 | E-GEOD-37031 | biostudies-arrayexpress
2023-02-08 | GSE189600 | GEO
2023-03-01 | GSE204901 | GEO
2017-12-03 | GSE104098 | GEO
2016-07-03 | E-GEOD-51389 | biostudies-arrayexpress