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Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Regulation of Nuclear Protein Sorting01:45

Regulation 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...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
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Related Experiment Video

Updated: Jun 8, 2026

Isolating Brown Adipocytes from Murine Interscapular Brown Adipose Tissue for Gene and Protein Expression Analysis
07:07

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Published on: March 12, 2021

Human NPC1L1 expression is positively regulated by PPARα.

Yuki Iwayanagi1, Tappei Takada, Fumiya Tomura

  • 1Department of Pharmacy, The University of Tokyo Hospital Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Pharmaceutical Research
|October 19, 2010
PubMed
Summary

Peroxisome proliferator-activated receptor alpha (PPARα) directly regulates human Niemann-Pick C1-like 1 (NPC1L1) gene transcription. PPARα and PGC1α co-transactivation offers insights into glucose, fatty acid, and cholesterol metabolism.

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Published on: January 6, 2023

Area of Science:

  • Molecular Biology
  • Metabolic Regulation
  • Gene Transcription

Background:

  • Niemann-Pick C1-like 1 (NPC1L1) is crucial for cholesterol absorption in enterocytes and hepatocytes.
  • NPC1L1 is a key pharmacological target for cholesterol-lowering drugs like ezetimibe.
  • The transcriptional regulation of NPC1L1 is not fully understood.

Purpose of the Study:

  • To investigate the role of peroxisome proliferator-activated receptor alpha (PPARα) in the transcriptional regulation of human NPC1L1.
  • To determine the involvement of PPARα coactivator 1α (PGC1α) in NPC1L1 gene expression.
  • To identify potential regulatory elements within the human NPC1L1 gene promoter.

Main Methods:

  • Reporter gene assays were used to assess promoter activity.
  • Electrophoretic mobility shift assays (EMSAs) confirmed direct binding of transcription factors.
  • siRNA-mediated knockdown of PPARα was employed to evaluate its effect on NPC1L1 expression.
  • Deletion and mutation analyses of the NPC1L1 promoter were performed.

Main Results:

  • PPARα significantly transactivated the human NPC1L1 promoter.
  • A functional PPARα-response element (PPRE) was identified in the -846/-834 region of the NPC1L1 gene.
  • Direct binding of PPARα and RXRα to the PPRE was confirmed by EMSA.
  • Knockdown of PPARα led to decreased NPC1L1 mRNA and protein levels in HepG2 cells.
  • PGC1α cotransfection enhanced NPC1L1 promoter activation mediated by SREBP2/HNF4α and PPARα/RXRα.

Conclusions:

  • PPARα positively regulates human NPC1L1 transcription through direct binding to a PPRE.
  • PGC1α coactivates the transcriptional regulation of human NPC1L1 by both SREBP2/HNF4α and PPARα/RXRα.
  • These findings elucidate a link between PPARα, PGC1α, and NPC1L1, contributing to understanding glucose, fatty acid, and cholesterol homeostasis.