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YY1 对肝脏脂质代谢的多方面调节。

Multifaceted regulation of hepatic lipid metabolism by YY1.

机构信息

Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

出版信息

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

DOI:10.26508/lsa.202000928
PMID:34099540
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8200296/
Abstract

Recent studies suggested that dysregulated 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 and , encoding key enzymes in lipogenesis, were regulated by the cooperation between YY1 and PPARA/RXRA complex over their promoters.

摘要

最近的研究表明，失调的 在许多肝脏疾病中起着关键作用。为了获得 YY1 在肝脏中调控的基因和途径的详细信息，我们在 HepG2 细胞中进行了 RNA 测序，在 YY1 敲低后进行了比较。通过比较 YY1 敲低样本（n = 8）和对照样本（n = 14），我们确定了一组严格的 2081 个差异表达基因。YY1 敲低显著降低了几个关键转录因子及其在脂质代谢中的共激活因子的表达。这是通过 YY1 通过结合其启动子和增强子区域来调节 PPARA 的表达来说明的。我们的研究进一步表明，关键转录因子的下调以及 YY1 敲低显著降低了 YY1 和这些转录因子在各种调节区域之间的合作，这对于调节肝脂质代谢中基因的表达非常重要。这一发现得到了支持，即编码脂肪生成关键酶的 和 的表达受到 YY1 和 PPARA/RXRA 复合物在其启动子上的合作调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/bb815e177fd0/LSA-2020-00928_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/1ff04663f6fe/LSA-2020-00928_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/82666fd0822f/LSA-2020-00928_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/0bd9638b5ab5/LSA-2020-00928_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/2601a4acec21/LSA-2020-00928_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/134d55547405/LSA-2020-00928_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/e2c47d6eb35f/LSA-2020-00928_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/c9edf7743eff/LSA-2020-00928_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/8fff5036a45e/LSA-2020-00928_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/42df6e764649/LSA-2020-00928_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/573b998a618c/LSA-2020-00928_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/e354faec5dd5/LSA-2020-00928_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/caa7bc7f0cc0/LSA-2020-00928_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/bb815e177fd0/LSA-2020-00928_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/1ff04663f6fe/LSA-2020-00928_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/82666fd0822f/LSA-2020-00928_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/0bd9638b5ab5/LSA-2020-00928_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/2601a4acec21/LSA-2020-00928_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/134d55547405/LSA-2020-00928_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/e2c47d6eb35f/LSA-2020-00928_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/c9edf7743eff/LSA-2020-00928_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/8fff5036a45e/LSA-2020-00928_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/42df6e764649/LSA-2020-00928_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/573b998a618c/LSA-2020-00928_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/e354faec5dd5/LSA-2020-00928_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/caa7bc7f0cc0/LSA-2020-00928_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fc3/8200296/bb815e177fd0/LSA-2020-00928_Fig10.jpg

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