title: RXRα and LXR activate two promoters in placenta- and tumor-specific expression of PLAC1.
abstract: PLAC1 expression, first characterized as restricted to developing placenta among normal tissues, is also found in a wide range of tumors and transformed cell lines. To understand the basis for its unusual expression profile, we have analyzed the gene structure and its mode of transcription. We find that the gene has a hitherto unique feature, with two promoters, P1 and P2, separated by 105 kb. P2 has been described before. Here we define P1 and show that it and P2 are activated by RXRα in conjunction with LXRα or LXRβ. In placenta, P2 is the preferred promoter, whereas various tumor cell lines tend to express predominantly either one or the other promoter. Furthermore, when each promoter is fused to a luciferase reporter gene and transfected into cancer cell lines, the promoter corresponding to the more active endogenous promoter is preferentially transcribed. Joint expression of activating nuclear receptors can partially account for the restricted expression of PLAC1 in placenta, and may be co-opted for preferential P1 or P2 PLAC1 expression in various tumor cells.
authors.affiliation: Laboratory of Genetics, National Institute on Aging, Bayview Research Center, 251 Bayview Blvd, RM 10B117, Baltimore, MD 21224, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Moradin
authors.forename: D
authors.initials: D
authors.lastname: Schlessinger
authors.forename: R
authors.initials: R
authors.lastname: Nagaraja
mesh_terms: D000818:Animals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000071518:Liver X Receptors; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D057093:Orphan Nuclear Receptors / Q000378:metabolism / Q000502:physiology*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D047490:Retinoid X Receptor alpha / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; C415583:PLAC1 protein, human; D011257:Pregnancy Proteins; D047490:Retinoid X Receptor alpha