Function Annotation of Hepatic Retinoid x Receptor α Based on Genome-Wide DNA Binding and Transcriptome Profiling
View/ Open
Issue Date
2012-11-15Author
Zhan, Qi
Fang, Yaping
He, Yuqi
Liu, Hui-Xin
Fang, Jianwen
Wan, Yu-Jui Yvonne
Publisher
Public LIbrary of Science
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
© 2012 Zhan 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.
Metadata
Show full item recordAbstract
BackgroundRetinoid 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-throughput manner.Principal FindingsClose to 80% of hepatic expressed genes were bound by RXRα, while 16% were expressed in an RXRα-dependent manner. Motif analysis predicted direct repeat with a spacer of one nucleotide as the most prevalent RXRα binding site. Many of the 500 strongest binding motifs overlapped with the binding motif of specific protein 1. Biological functional analysis of RXRα-dependent genes revealed that hepatic RXRα 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, RXRα bound to many genes that encode nuclear receptors and their cofactors suggesting the central role of RXRα in regulating nuclear receptor-mediated pathways.ConclusionsThis study establishes the relationship between RXRα DNA binding and hepatic gene expression. RXRα binds extensively to the mouse genome. However, DNA binding does not necessarily affect the basal mRNA level. In addition to metabolism, RXRα dictates the expression of genes that regulate RNA processing, translation, and protein folding illustrating the novel roles of hepatic RXRα in post-transcriptional regulation.
Collections
Citation
Zhan, Q., Fang, Y., He, Y., Liu, H.-X., Fang, J., & Wan, Y.-J. Y. (2012). Function Annotation of Hepatic Retinoid x Receptor α Based on Genome-Wide DNA Binding and Transcriptome Profiling. PLoS ONE, 7(11). http://dx.doi.org/10.1371/journal.pone.0050013
Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.
Except where otherwise noted, this item's license is described as: © 2012 Zhan 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.