title: Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophages.
abstract: 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.
authors.affiliation: School of Medicine, Institute of Biomedicine, University of Eastern Finland, FIN-70210 Kuopio, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Pehkonen
authors.forename: Lynn
authors.initials: L
authors.lastname: Welter-Stahl
authors.forename: Janine
authors.initials: J
authors.lastname: Diwo
authors.forename: Jussi
authors.initials: J
authors.lastname: Ryynänen
authors.forename: Anke
authors.initials: A
authors.lastname: Wienecke-Baldacchino
authors.forename: Sami
authors.initials: S
authors.lastname: Heikkinen
authors.forename: Eckardt
authors.initials: E
authors.lastname: Treuter
authors.forename: Knut R
authors.initials: KR
authors.lastname: Steffensen
authors.forename: Carsten
authors.initials: C
authors.lastname: Carlberg
mesh_terms: D017209:Apoptosis; D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D050356:Lipid Metabolism; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding; D015854:Up-Regulation
chemical_list: D002843:Chromatin; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors