title: Dynamic regulation of alternative ATP-binding cassette transporter A1 transcripts.
abstract: The ATP-binding cassette transporter A1 (ABCA1) gene, a major regulator of high-density lipoprotein (HDL) metabolism, utilizes several transcriptional start sites. The pattern of transcripts among tissues and cells differed significantly. The longest (class 1) transcripts were abundant in adult brain and fetal tissues. Class 2 transcripts predominated in most other tissues. The shortest (class 3) transcripts were present mainly in adult liver and lung. To study the biochemical significance of changes in transcript distribution, two cell models were compared. In primary human fibroblasts, upregulation of mRNA levels by oxysterols and retinoic acid increased the relative proportion of class 2 transcript compared to class 1. Phorbol ester stimulated human macrophage-derived THP-1 cells increased the abundance of class 1 transcripts relative to class 2. In both cell lines class 3 transcript levels were minimal and unchanged. It is shown here for the first time that the regulation of ABCA1 mRNA levels exploits the use of alternative transcription start sites.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0130, USA. jhuu6676@itsa.ucsf.edu
authors.forename: Jarkko
authors.initials: J
authors.lastname: Huuskonen
authors.forename: Monika
authors.initials: M
authors.lastname: Abedin
authors.forename: Meeta
authors.initials: M
authors.lastname: Vishnu
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Baranzini
authors.forename: John P
authors.initials: JP
authors.lastname: Kane
authors.forename: Phoebe E
authors.initials: PE
authors.lastname: Fielding
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fielding
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005091:Exons; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D010703:Phorbol Esters / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013261:Sterols / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014212:Tretinoin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008075:Lipoproteins, HDL; D010703:Phorbol Esters; D012333:RNA, Messenger; D013261:Sterols; D014212:Tretinoin