Multifaceted regulation of hepatic lipid metabolism by YY1

Life Sci Alliance. 2021 Jun 7;4(7):e202000928. doi: 10.26508/lsa.202000928. Print 2021 Jul.

Abstract

Recent studies suggested that dysregulated YY1 plays a pivotal role in many liver diseases. To obtain a detailed view of genes and pathways regulated by YY1 in the liver, we carried out RNA sequencing in HepG2 cells after YY1 knockdown. A rigid set of 2,081 differentially expressed genes was identified by comparing the YY1-knockdown samples (n = 8) with the control samples (n = 14). YY1 knockdown significantly decreased the expression of several key transcription factors and their coactivators in lipid metabolism. This is illustrated by YY1 regulating PPARA expression through binding to its promoter and enhancer regions. Our study further suggest that down-regulation of the key transcription factors together with YY1 knockdown significantly decreased the cooperation between YY1 and these transcription factors at various regulatory regions, which are important in regulating the expression of genes in hepatic lipid metabolism. This was supported by the finding that the expression of SCD and ELOVL6, encoding key enzymes in lipogenesis, were regulated by the cooperation between YY1 and PPARA/RXRA complex over their promoters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Fatty Acid Elongases
  • Hep G2 Cells
  • Humans
  • Lipid Metabolism / genetics*
  • Lipid Metabolism / physiology
  • Liver / metabolism*
  • PPAR alpha / genetics
  • Promoter Regions, Genetic / genetics
  • Retinoid X Receptor alpha
  • Stearoyl-CoA Desaturase
  • Transcription Factors / genetics
  • YY1 Transcription Factor / genetics
  • YY1 Transcription Factor / metabolism*
  • YY1 Transcription Factor / physiology

Substances

  • ELOVL6 protein, human
  • PPAR alpha
  • RXRA protein, human
  • Retinoid X Receptor alpha
  • Transcription Factors
  • YY1 Transcription Factor
  • YY1 protein, human
  • SCD1 protein, human
  • Stearoyl-CoA Desaturase
  • Fatty Acid Elongases