Article (Scientific journals)
Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophages
Pehkonen, Petri; Welter-Stahl, Lynn; DIWO, Janine et al.
2012In BMC Genomics, 13 (50)
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Abstract :
[en] Background: The liver X receptors (LXRs) are oxysterol sensing nuclear receptors with multiple effects on metabolism and immune cells. However, the complete genome-wide cistrome of LXR in cells of human origin has not yet been provided. Results: We performed ChIP-seq in phorbol myristate acetate-differentiated THP-1 cells (macrophage-type) after stimulation with the potent synthetic LXR ligand T0901317 (T09). Microarray gene expression analysis was performed in the same cellular model. We identified 1357 genome-wide LXR locations (FDR < 1%), of which 526 were observed after T09 treatment. De novo analysis of LXR binding sequences identified a DR4-type element as the major motif. On mRNA level T09 up-regulated 1258 genes and repressed 455 genes. Our results show that LXR actions are focused on 112 genomic regions that contain up to 11 T09 target genes per region under the control of highly stringent LXR binding sites with individual constellations for each region. We could confirm that LXR controls lipid metabolism and transport and observed a strong association with apoptosis-related functions. Conclusions: This first report on genome-wide binding of LXR in a human cell line provides new insights into the transcriptional network of LXR and its target genes with their link to physiological processes, such as apoptosis. The gene expression microarray and sequence data have been submitted collectively to the NCBI Gene Expression Omnibus http://www.ncbi.nlm.nih.gov/geo under accession number GSE28319.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Pehkonen, Petri;  Institute of Biomedicine, University of Eastern Finland > School of Medicine
Welter-Stahl, Lynn;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
DIWO, Janine;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Ryynänen, Jussi;  Institute of Biomedicine, University of Eastern Finland > School of Medicine
WIENECKE-BALDACCHINO, Anke ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Heikkinen, Sami;  Institute of Biomedicine, University of Eastern Finland > School of Medicine
Treuter, Eckardt;  Karolinska Institutet > Department of Biosciences and Nutrition
Steffensen, Knut R;  Karolinska Institutet > Department of Biosciences and Nutrition
Carlberg, Carsten;  Institute of Biomedicine, University of Eastern Finland > School of Medicine
External co-authors :
yes
Language :
English
Title :
Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophages
Publication date :
2012
Journal title :
BMC Genomics
ISSN :
1471-2164
Publisher :
BioMed Central
Volume :
13
Issue :
50
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 30 March 2016

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