PXD026717

PXD026717 is an original dataset announced via ProteomeXchange.

Title	Discovery of lipotoxicity-sensitive transcription factors in non-alcoholic steatohepatitis
Description	Non-alcoholic fatty liver disease is continuum of disorders among which non-alcoholic steatohepatitis (NASH) is particularly associated with a negative prognosis. Hepatocyte lipotoxicity is one of the main pathogenic factors of liver fibrosis and NASH. However, the molecular mechanisms regulating this process are poorly understood. Here, we integrated transcriptomic and chromatin accessibility analyses from human liver and mouse hepatocytes to identify lipotoxicity-sensitive transcription factors. We found that the transcription factors MAFK and TCF4 were activated in liver from NASH patients and by mouse hepatocyte lipotoxicity. Genetic deletion of these transcription factors protected hepatocytes against saturated fatty acid oversupply. Notably, MAFK- and TCF4-regulated gene expression linked to lipotoxicity closely correlated with transcriptional patters in fibrosis progression in NASH patients. Collectively, our findings uncovered novel molecular insights into lipotoxicityinduced NASH, revealing the relevance and therapeutic potential of MAFK and TCF4 in human disease.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:53:15.621.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD026717
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Danilo Ritz
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-15 08:11:13	ID requested
1	2022-07-08 05:24:55	announced
⏵ 2	2023-11-14 08:53:16	announced	2023-11-14: Updated project metadata.

10.6019/PXD026717;

submitter keyword: TMT, transcription factor,non-alcoholic steatohepatitis

Alexander Schmidt
contact affiliation	Dr. Alexander Schmidt Proteomics Core Facility Biozentrum, University of Basel Klingelbergstrasse 50/70 CH-4056 Basel / Switzerland
contact email	alex.schmidt@unibas.ch
lab head
Danilo Ritz
contact affiliation	Proteomics Core Facility Biozentrum, University of Basel Klingelbergstrasse 50/70 CH-4056 Basel / Switzerland
contact email	danilo.ritz@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026717
     1. Label: PRIDE project
     2. Name: Discovery of lipotoxicity-sensitive transcription factors in non-alcoholic steatohepatitis