UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Date

6-5-2013

Document Type

Article

Medical Subject Headings

Gene Expression Regulation; Hep G2 Cells; Histone Demethylases

Disciplines

Genetics and Genomics | Molecular Biology | Molecular Genetics

Abstract

Aberrant gluconeogenic gene expression is associated with diabetes, glycogen storage disease, and liver cancer. However, little is known how these genes are regulated at the chromatin level. In this study, we investigated in HepG2 cells whether histone demethylation is a potential mechanism. We found that knockdown or pharmacological inhibition of histone demethylase LSD1 causes remarkable transcription activation of two gluconeogenic genes, FBP1 and G6Pase, and consequently leads to increased de novo glucose synthesis and decreased intracellular glycogen content. Mechanistically, LSD1 occupies the promoters of FBP1 and G6Pase, and modulates their H3K4 dimethylation levels. Thus, our work identifies an epigenetic pathway directly governing gluconeogenic gene expression, which might have important implications in metabolic physiology and diseases.

Rights and Permissions

Citation: PLoS One. 2013 Jun 5;8(6):e66294. doi: 10.1371/journal.pone.0066294. Print 2013. Link to article on publisher's site

Comments

Copyright: © 2013 Pan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Related Resources

Link to Article in PubMed

PubMed ID

23755305

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