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In Situ Saturating Mutagenesis Screening Identifies a Functional Genomic Locus that Regulates Ucp1 Expression
Yan Qiu1, Xiaojian Liu1, Yingmin Sun1
1CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031 People's Republic of China.
Phenomics (Cham, Switzerland)
|March 20, 2023
Summary
Researchers identified key DNA regions controlling UCP1 gene expression in fat cells using CRISPR-Cas9 screening. This advances understanding of thermogenesis for potential obesity treatments.
Area of Science:
- Molecular Biology
- Genetics
- Metabolic Diseases
Background:
- Understanding UCP1 gene regulation in brown and beige adipocytes is crucial for developing obesity treatments.
- Targeting adipose cell fate and thermogenesis offers therapeutic potential for metabolic disorders.
Purpose of the Study:
- To systematically identify cis-regulatory elements controlling UCP1 expression.
- To explore the molecular mechanisms underlying UCP1 gene regulation.
Main Methods:
- Utilized a high-throughput CRISPR-Cas9 screening system for in situ saturating mutagenesis.
- Employed a customized sgRNA library targeting a ~20 kb genomic region near the UCP1 gene.
- Conducted screening in cultured brown and white adipocytes in vitro and in inguinal white adipose tissue in vivo.
Main Results:
- Identified several genomic loci containing key regulatory elements for UCP1 expression.
- Demonstrated the effectiveness of the screening approach in identifying cis-regulatory elements.
- Provided insights into the transcriptional regulation of UCP1 in different adipose tissues.
Conclusions:
- The study successfully identified novel cis-regulatory elements influencing UCP1 expression.
- Highlights a broadly applicable high-throughput method for cis-regulatory element discovery.
- Findings contribute to understanding thermogenesis and offer potential avenues for obesity therapeutics.
