Dataset Information

Function annotation of hepatic retinoid x receptor ? based on genome-wide DNA binding and transcriptome profiling.

ABSTRACT:

Background

Retinoid x receptor ? (RXR?) is abundantly expressed in the liver and is essential for the function of other nuclear receptors. Using chromatin immunoprecipitation sequencing and mRNA profiling data generated from wild type and RXR?-null mouse livers, the current study identifies the bona-fide hepatic RXR? targets and biological pathways. In addition, based on binding and motif analysis, the molecular mechanism by which RXR? regulates hepatic genes is elucidated in a high-throughput manner.

Principal findings

Close to 80% of hepatic expressed genes were bound by RXR?, while 16% were expressed in an RXR?-dependent manner. Motif analysis predicted direct repeat with a spacer of one nucleotide as the most prevalent RXR? binding site. Many of the 500 strongest binding motifs overlapped with the binding motif of specific protein 1. Biological functional analysis of RXR?-dependent genes revealed that hepatic RXR? deficiency mainly resulted in up-regulation of steroid and cholesterol biosynthesis-related genes and down-regulation of translation- as well as anti-apoptosis-related genes. Furthermore, RXR? bound to many genes that encode nuclear receptors and their cofactors suggesting the central role of RXR? in regulating nuclear receptor-mediated pathways.

Conclusions

This study establishes the relationship between RXR? DNA binding and hepatic gene expression. RXR? binds extensively to the mouse genome. However, DNA binding does not necessarily affect the basal mRNA level. In addition to metabolism, RXR? dictates the expression of genes that regulate RNA processing, translation, and protein folding illustrating the novel roles of hepatic RXR? in post-transcriptional regulation.

SUBMITTER: Zhan Q

PROVIDER: S-EPMC3499475 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Function annotation of hepatic retinoid x receptor α based on genome-wide DNA binding and transcriptome profiling.

Zhan Qi Q Fang Yaping Y He Yuqi Y Liu Hui-Xin HX Fang Jianwen J Wan Yu-Jui Yvonne YJ

PloS one 20121115 11

<h4>Background</h4>Retinoid x receptor α (RXRα) is abundantly expressed in the liver and is essential for the function of other nuclear receptors. Using chromatin immunoprecipitation sequencing and mRNA profiling data generated from wild type and RXRα-null mouse livers, the current study identifies the bona-fide hepatic RXRα targets and biological pathways. In addition, based on binding and motif analysis, the molecular mechanism by which RXRα regulates hepatic genes is elucidated in a high-thro ...[more]

PMID: 23166811

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