Regulation of lipogenic gene expression by lysine-specific histone demethylase-1 (LSD1)

Arian Abdulla, Yi Zhang, Fu Ning Hsu, Alus Michael Xiaoli, Xiaoping Zhao, Ellen S T Yang, Jun Yuan Ji, Fajun Yang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Dysregulation of lipid homeostasis is a common feature of several major human diseases, including type 2 diabetes and cardiovascular disease. However, because of the complex nature of lipid metabolism, the regulatory mechanisms remain poorly defined at the molecular level. As the key transcriptional activators of lipogenic genes, such as fatty acid synthase (FAS), sterol regulatory element-binding proteins (SREBPs) play a pivotal role in stimulating lipid biosynthesis. Several studies have shown that SREBPs are regulated by the NAD+-dependent histone deacetylase SIRT1, which forms a complex with the lysine-specific histone demethylase LSD1. Here, we show that LSD1 plays a role in regulating SREBP1-mediated gene expression. Multiple lines of evidence suggest that LSD1 is required for SREBP1-dependent activation of the FAS promoter in mammalian cells. LSD1 knockdown decreases SREBP-1a at the transcription level. Although LSD1 affects nuclear SREBP-1 abundance indirectly through SIRT1, it is also required for SREBP1 binding to the FAS promoter. As a result, LSD1 knockdown decreases triglyceride levels in hepatocytes. Taken together, these results show that LSD1 plays a role in regulating lipogenic gene expression, suggesting LSD1 as a potential target for treating dysregulation of lipid metabolism.

Original languageEnglish (US)
Pages (from-to)29937-29947
Number of pages11
JournalJournal of Biological Chemistry
Volume289
Issue number43
DOIs
StatePublished - Oct 24 2014

Fingerprint

Histone Demethylases
Gene Expression Regulation
Gene expression
Lysine
Fatty Acid Synthases
Sterol Regulatory Element Binding Proteins
Sterol Regulatory Element Binding Protein 1
Lipid Metabolism
Lipids
Gene Expression
Histone Deacetylases
Biosynthesis
Transcription
Medical problems
NAD
Type 2 Diabetes Mellitus
Hepatocytes
Triglycerides
Homeostasis
Cardiovascular Diseases

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Regulation of lipogenic gene expression by lysine-specific histone demethylase-1 (LSD1). / Abdulla, Arian; Zhang, Yi; Hsu, Fu Ning; Xiaoli, Alus Michael; Zhao, Xiaoping; Yang, Ellen S T; Ji, Jun Yuan; Yang, Fajun.

In: Journal of Biological Chemistry, Vol. 289, No. 43, 24.10.2014, p. 29937-29947.

Research output: Contribution to journalArticle

Abdulla, Arian ; Zhang, Yi ; Hsu, Fu Ning ; Xiaoli, Alus Michael ; Zhao, Xiaoping ; Yang, Ellen S T ; Ji, Jun Yuan ; Yang, Fajun. / Regulation of lipogenic gene expression by lysine-specific histone demethylase-1 (LSD1). In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 43. pp. 29937-29947.
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