Genomic structure and mapping of human orphan receptor LXR alpha: upregulation of LXRa mRNA during monocyte to macrophage differentiation.
In order to identify changes in the gene expression profile during human monocyte/macrophage differentiation in the presence of GM-CSF, the expression level of various mRNA was studied using DNA microarray technology. We found LXR alpha (LXRa) to be the most highly induced transcriptional regulator during macrophage differentiation. The LXRa mRNA level was induced 40 fold which ranked it as the 10th highest among the approximately 5,600 genes studied. Although only restricted hepatic expression of LXRa mRNA had been reported, the macrophage expressed the highest level of LXRa among the nine human tissues and cultured cells studied. To further investigate transcriptional control, we have characterized the genomic structure of the human LXRa gene and determined the structure of its promoter region. The human LXRa gene consists of eleven exons, and analysis of the promoter region indicated the presence of conserved binding sites for myeloid zinc finger protein 1, which may be related to the extrahepatic expression of LXRa. LXRa is known to be activated by oxysterols, and the induced expression of the gene may be related to the foam cell formation in atherosclerotic lesions.
Kohro
T
T
Department of Molecular Biology and Medicine, The University of Tokyo, Japan.
Nakajima
T
T
Wada
Y
Y
Sugiyama
A
A
Ishii
M
M
Tsutsumi
S
S
Aburatani
H
H
Imoto
I
I
Inazawa
J
J
Hamakubo
T
T
Kodama
T
T
Emi
M
M
D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002874:Chromosome Mapping; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D000071518:Liver X Receptors; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D057093:Orphan Nuclear Receptors; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014018:Tissue Distribution; D015854:Up-Regulation / Q000187:drug effects
D017931:DNA Primers; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D016178:Granulocyte-Macrophage Colony-Stimulating Factor