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Identification of Functional Transcriptional Binding Sites within Chicken Abcg2 Gene Promoter and Screening Its

Yujuan Zhang1,2, Jinhu Huang1, Xiangxiu Li1

  • 1MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.

Genes
|February 14, 2020
PubMed

Insights

Researchers identified regulatory mechanisms for chicken Abcg2 gene expression, crucial for understanding drug pharmacokinetics and developing veterinary medicines. This study characterized the Abcg2 promoter and its response to xenobiotics.

Area of Science:

  • Molecular Biology
  • Pharmacology
  • Genomics

Background:

  • Breast cancer resistance protein (BCRP) is an ABC transporter affecting drug pharmacokinetics.
  • The chicken Abcg2 gene encodes BCRP, and its transcriptional regulation is not fully understood.

Purpose of the Study:

  • To clone and characterize the promoter region of the chicken Abcg2 gene.
  • To elucidate the regulatory mechanisms controlling chicken Abcg2 gene transcription.
  • To investigate the impact of xenobiotics on Abcg2 gene expression and BCRP function.

Main Methods:

  • Cloning and characterization of the chicken Abcg2 promoter region.
  • Luciferase reporter assays in LMH cells and primary hepatocytes.
  • RT-PCR, drug accumulation analysis, and progressive deletion/mutation assays.

Main Results:

  • The chicken Abcg2 gene possesses a TATA-less promoter with Sp1 sites and CpG islands.
  • A basal promoter (-110 to +30) drives constitutive Abcg2 expression.
  • Daidzein, clotrimazole, ivermectin, and LPS significantly regulate the Abcg2 promoter, affecting BCRP expression and function.

Conclusions:

  • The study identified key regulatory elements and domains within the chicken Abcg2 promoter.
  • Xenobiotics modulate chicken Abcg2 gene expression and BCRP activity through promoter regulation.
  • Findings provide insights into veterinary drug development and usage by understanding Abcg2 regulation.
Keywords:
LMHchicken Abcg2primary hepatocytespromoterregulators

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