Related Experiment Video
Updated: Jun 5, 2026
09:15
Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC
Published on: May 9, 2020
A nutrient-sensitive interaction between Sirt1 and HNF-1α regulates Crp expression
Andrew A Grimm1, Cynthia S Brace, Ting Wang
1Department of Developmental Biology Department of Genetics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Aging Cell
|December 24, 2010
Summary
Nutrient restriction activates a novel interaction between Sirt1 and HNF-1α, suppressing C-reactive protein (Crp) gene expression and revealing mechanisms of diet restriction
Area of Science:
- Cellular and Molecular Biology
- Genetics and Epigenetics
- Metabolism and Aging
Background:
- Silent information regulator 2 (Sir2) orthologs are NAD-dependent deacetylases regulating aging.
- Sirtuin 1 (Sirt1) is a mammalian Sir2 ortholog involved in metabolic and stress responses.
- Understanding Sirt1's gene expression control during nutrient availability is crucial.
Purpose of the Study:
- To identify novel Sirt1 interacting partners and elucidate its mechanism in controlling gene expression.
- To investigate the role of HNF-1α as a potential Sirt1 target in nutrient response.
Main Methods:
- Bioinformatic screening combining gene expression analysis and phylogenetic footprinting.
- In vitro and in vivo interaction studies between Sirt1 and HNF-1α.
- Analysis of C-reactive protein (Crp) gene expression and histone acetylation in hepatocytes.
Main Results:
- Sirt1 interacts with HNF-1α in vivo under nutrient-restricting conditions, requiring 12-24 hours and protein synthesis.
- Both nutrient restriction and Sirt1 suppress HNF-1α transcriptional activity and Crp expression.
- Sirt1 and HNF-1α co-localize on the Crp promoter, decreasing histone H4 acetylation.
Conclusions:
- A novel nutrient-dependent interaction between Sirt1 and HNF-1α is revealed.
- This interaction mediates the suppression of Crp gene expression by nutrient restriction.
- Provides insight into Sirt1's role in mediating the anti-aging effects of diet restriction.
Related Concept Videos
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:28Global Regulatory Systems
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
01:29Translational Regulation
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...