Related Experiment Video
Updated: Jun 10, 2026
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
A single-nucleotide variation in a p53-binding site affects nutrient-sensitive human SIRT1 expression.
Asma Naqvi1, Timothy A Hoffman, Jeremy DeRicco
1Cardiovascular Institute, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Human Molecular Genetics
|August 10, 2010
Summary
A novel single-nucleotide variation in the SIRT1 promoter impacts nutrient-sensitive gene expression. This finding reveals how calorie restriction affects metabolism via SIRT1 (SIRTUIN1) and its target genes.
Area of Science:
- Metabolic regulation
- Molecular biology
- Genetics
Background:
- SIRTUIN1 (SIRT1) is a deacetylase crucial for nutrient sensing and metabolic regulation in mammals.
- SIRT1 expression is typically repressed by p53 through response elements in its promoter.
- Understanding the regulation of SIRT1 is key to comprehending metabolic adaptation.
Purpose of the Study:
- To identify novel regulatory elements in the human SIRT1 promoter.
- To investigate the role of a specific single-nucleotide polymorphism (SNP) in SIRT1 regulation.
- To elucidate the impact of this SNP on nutrient-sensitive transcription and calorie restriction responses.
Main Methods:
- Identification of a novel p53-binding sequence in the distal human SIRT1 promoter.
- Analysis of a common C/T single-nucleotide variation within this binding sequence.
- Investigation of promoter occupancy by p53 and Hypermethylated-In-Cancer-1 (HIC1) under nutrient deprivation.
- Assessment of SIRT1 and target gene expression (AMPKα2, PGC-1β) in response to calorie restriction.
Main Results:
- A novel p53-binding sequence in the distal SIRT1 promoter was identified, essential for nutrient-sensitive transcription.
- A common C/T SNP in this sequence affects nutrient deprivation-induced SIRT1 transcription and calorie restriction-induced expression.
- The C variation impairs p53 binding and reduces the promoter's nutrient sensitivity compared to the T variation.
- HIC1 and p53 were found to compete for binding to this promoter region, with nutrient deprivation favoring p53 occupancy.
Conclusions:
- A common SNP in the human SIRT1 promoter influences nutrient-sensitive SIRT1 expression.
- This genetic variation impacts calorie restriction-mediated metabolic and physiological changes.
- The findings highlight the significance of genetic variation in metabolic regulation by SIRT1.
More Related Videos
Related Concept Videos
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:16Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
02:30Histone Variants at the Centromere
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
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...