Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophages
1 School of Medicine, Institute of Biomedicine, University of Eastern Finland, FIN-70210 Kuopio, Finland
2 Life Sciences Research Unit, University of Luxembourg, L-1511 Luxembourg, Luxembourg
3 Department of Biosciences and Nutrition, Karolinska Institutet, S-14183 Huddinge, Sweden
BMC Genomics 2012, 13:50 doi:10.1186/1471-2164-13-50Published: 31 January 2012
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.
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.
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.