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Status |
Public on Apr 06, 2022 |
Title |
A hierarchical regulatory network ensures stable albumin transcription under various pathophysiological conditions |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Physiologically, albumin is produced by hepatocytes. It remains largely unknown how patients are capable of maintaining essential albumin levels even in the condition of liver failure. Here, we delineate a hierarchical regulatory network that controls albumin transcription under different pathophysiological conditions. The ALB core promoter possesses a TATA box and nucleosome-free area, which allows constitutive binding of RNA Pol II and thus initiation of transcription. In normal conditions, HNF4α and C/EBPα facilitate albumin transcription through binding to its promoter. In severely damaged livers, hepatocellular HNF4α and C/EBPα expression is often inhibited. The absence of HNF4 and C/EBPα increases hedgehog ligand biosynthesis. Hedgehog upregulates FOXA2 expression through transcription factor GLI2 binding to the FOXA2 promoter. Subsequently, FOXA2 maintains albumin expression in the hepatocytes lacking HNF4α and C/EBPα. In patients with massive hepatocyte loss, the expression of albumin is activated in liver progenitor cells. Albumin transcription in these cells is regulated by HNF4α or FOXA2. Taken together, HNF4α, C/EBPα and FOXA2 form a hierarchical regulatory network that ensures stable albumin expression even in pathophysiological conditions.
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Overall design |
Mouse primary hepatocytes (MPH) were freshly isolated from three mice: Mouse1, Mouse2, Mouse3. RNA sequencing was performed in MPH with or without HNF4α and C/EBPα siRNA treatment for 48 hours.
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Contributor(s) |
Weng H |
Citation(s) |
35257388 |
Submission date |
Jul 30, 2021 |
Last update date |
Apr 08, 2022 |
Contact name |
Carsten Sticht |
Organization name |
University Heidelberg
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Department |
ZMF
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Street address |
Theodor-Kutzer-Ufer
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City |
Mannheim |
ZIP/Postal code |
68169 |
Country |
Germany |
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Platforms (1) |
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Samples (12)
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Relations |
BioProject |
PRJNA751052 |
SRA |
SRP330566 |