RT Journal Article
SR Electronic
T1 Multifaceted regulation of hepatic lipid metabolism by YY1
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000928
DO 10.26508/lsa.202000928
VO 4
IS 7
A1 Gang Pan
A1 Klev Diamanti
A1 Marco Cavalli
A1 Ariadna Lara Gutiérrez
A1 Jan Komorowski
A1 Claes Wadelius
YR 2021
UL https://www.life-science-alliance.org/content/4/7/e202000928.abstract
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.