PT  - JOURNAL ARTICLE
AU  - Gang Pan
AU  - Klev Diamanti
AU  - Marco Cavalli
AU  - Ariadna Lara Gutiérrez
AU  - Jan Komorowski
AU  - Claes Wadelius
TI  - Multifaceted regulation of hepatic lipid metabolism by YY1
AID  - 10.26508/lsa.202000928
DP  - 2021 Jul 01
TA  - Life Science Alliance
PG  - e202000928
VI  - 4
IP  - 7
4099  - https://www.life-science-alliance.org/content/4/7/e202000928.short
4100  - https://www.life-science-alliance.org/content/4/7/e202000928.full
SO  - Life Sci. Alliance2021 Jul 01; 4
AB  - 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.