Genome-wide binding of the orphan nuclear receptor TR4 suggests its general role in fundamental biological processes

BMC Genomics

Research Article

Maureen A Sartor¹  Osamu Tanabe²  Lihong Shi²  James D Engel²  Yu-Hsuan Lin³  Peggy J Farnham⁴  Daniel He⁴  Xiaoqin Xu⁴  Lorigail Echipare⁴  Henriette O'Geen⁴  Vitalina M Komashko⁴  Seth Frietze⁴ 

[1] Center for Computational Medicine and Bioinformatics, University of Michigan Medical School, 48109, Ann Arbor, MI, USA;Department of Cell and Developmental Biology, University of Michigan Medical School, 48109, Ann Arbor, MI, USA;Department of Cell and Developmental Biology, University of Michigan Medical School, 48109, Ann Arbor, MI, USA;Center for Computational Medicine and Bioinformatics, University of Michigan Medical School, 48109, Ann Arbor, MI, USA;Genome Center, University of California at Davis, 95616, Davis, CA, USA;

关键词: HepG2 Cell;    GM12878 Cell;    Fundamental Biological Process;    Motif Discovery Program;    StaphA Cell;   

DOI  :  10.1186/1471-2164-11-689

 received in 2010-07-12, accepted in 2010-12-02,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe orphan nuclear receptor TR4 (human testicular receptor 4 or NR2C2) plays a pivotal role in a variety of biological and metabolic processes. With no known ligand and few known target genes, the mode of TR4 function was unclear.ResultsWe report the first genome-wide identification and characterization of TR4 in vivo binding. Using chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq), we identified TR4 binding sites in 4 different human cell types and found that the majority of target genes were shared among different cells. TR4 target genes are involved in fundamental biological processes such as RNA metabolism and protein translation. In addition, we found that a subset of TR4 target genes exerts cell-type specific functions. Analysis of the TR4 binding sites revealed that less than 30% of the peaks from any of the cell types contained the DR1 motif previously derived from in vitro studies, suggesting that TR4 may be recruited to the genome via interaction with other proteins. A bioinformatics analysis of the TR4 binding sites predicted a cis regulatory module involving TR4 and ETS transcription factors. To test this prediction, we performed ChIP-seq for the ETS factor ELK4 and found that 30% of TR4 binding sites were also bound by ELK4. Motif analysis of the sites bound by both factors revealed a lack of the DR1 element, suggesting that TR4 binding at a subset of sites is facilitated through the ETS transcription factor ELK4. Further studies will be required to investigate the functional interdependence of these two factors.ConclusionsOur data suggest that TR4 plays a pivotal role in fundamental biological processes across different cell types. In addition, the identification of cell type specific TR4 binding sites enables future studies of the pathways underlying TR4 action and its possible role in metabolic diseases.

【 授权许可】

Unknown   
© O'Geen et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.