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Involvement of Liver X Receptor Alpha in Histone Modifications Across the Target Fatty Acid Synthase Gene

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Lipids

Abstract

The liver X receptor alpha (LXRα), a member of the nuclear receptor superfamily, has been shown to regulate the expression of the fatty acid synthase (FAS) gene through direct interaction with the FAS promoter. However, its regulation of gene expression is not completely understood. Histone modifications and chromatin remodeling are closely linked to transcriptional activation of genes. In the present study, we examined the effect of LXRα activation or silencing on histone modifications (i.e., acetylation, methylation, and phosphorylation) across the FAS gene, with the aim to investigate whether LXRα could regulate its target gene expression at the epigenetic level. The addition of LXR agonist T0901317 or ectopic expression of LXRα stimulated the FAS transcription, which was coupled with increased levels of histones H3 and H4 acetylation and H3 phosphorylation and methylation at the LXR response element (LXRE). LXR ligation or overexpression induced distinct histone modification patterns at the distal region 2,272 bp upstream from the transcription start site (TSS) and TSS of the FAS gene. Moreover, RNA interference-mediated downregulation of LXRα impaired the histone acetylation and methylation but not phosphorylation on the FAS gene. In conclusion, we provide evidence that LXRα ligation-mediated transcriptional activation of the FAS gene is associated with LXRα-dependent histone acetylation and methylation rather than phosphorylation on this target gene.

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Abbreviations

ASC-2:

Activating signal cointegrator-2

ChIP:

Chromatin immunoprecipitation

FAS:

Fatty acid synthase

FXR:

Farnesoid X-receptor

LXR:

Liver X receptor

LXRE:

LXR response element

qRT-PCR:

Quantitative real-time PCR

TSS:

Transcription start site

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Acknowledgments

This work was supported by the Natural Science Foundation of China (30871160).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Digestive Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China

    Huihong Yu, Jinjun Guo, Yingxia Xiang, Jie Cao & Wei Shen

  2. Department of Digestive Diseases, The Fifth People’s Hospital of Shenzhen, Shenzhen, China

    Jinfeng Wu

  3. The Third People’s Hospital of Chengdu, Chengdu, China

    Mei Yang

  4. Department of Digestive Diseases, Chongqing General Hospital of Chinese Armed Police, Chongqing, China

    Lili Zheng

  5. Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China

    Mingli Peng

  6. Department of Digestive Diseases, The First People’s Hospital of Liangshan, Liangshan, China

    Qin Zhang

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  1. Huihong Yu
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Correspondence to Wei Shen.

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Yu, H., Wu, J., Yang, M. et al. Involvement of Liver X Receptor Alpha in Histone Modifications Across the Target Fatty Acid Synthase Gene. Lipids 47, 249–257 (2012). https://doi.org/10.1007/s11745-011-3635-0

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  • DOI: https://doi.org/10.1007/s11745-011-3635-0

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