Function Annotation of Hepatic Retinoid x Receptor α Based on Genome-Wide DNA Binding and Transcriptome Profiling
dc.contributor.author | Zhan, Qi | |
dc.contributor.author | Fang, Yaping | |
dc.contributor.author | He, Yuqi | |
dc.contributor.author | Liu, Hui-Xin | |
dc.contributor.author | Fang, Jianwen | |
dc.contributor.author | Wan, Yu-Jui Yvonne | |
dc.date.accessioned | 2014-03-20T18:28:51Z | |
dc.date.available | 2014-03-20T18:28:51Z | |
dc.date.issued | 2012-11-15 | |
dc.identifier.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 | |
dc.identifier.uri | http://hdl.handle.net/1808/13315 | |
dc.description.abstract | 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. | |
dc.description.sponsorship | This work was supported by the National Institutes of Health (DK092100 and CA053596 to YYW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | |
dc.publisher | Public LIbrary of Science | |
dc.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. | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Binding Analysis | |
dc.subject | DNA Transcription | |
dc.subject | Gene Expression | |
dc.subject | Gene Regulation | |
dc.subject | Hepatocytes | |
dc.subject | Mammalian Genomics | |
dc.subject | Metabolic Processes | |
dc.subject | Sequence Motif Analysis | |
dc.title | Function Annotation of Hepatic Retinoid x Receptor α Based on Genome-Wide DNA Binding and Transcriptome Profiling | |
dc.type | Article | |
kusw.kuauthor | Fang, Yaping | |
kusw.kuauthor | Fang, Jianwen | |
kusw.kudepartment | Applied Bioinformatics Laboratory, | |
kusw.oastatus | fullparticipation | |
dc.identifier.doi | 10.1371/journal.pone.0050013 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item meets KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess |
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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.