Dynamic regulation of alternative ATP-binding cassette transporter A1 transcripts.
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.
Huuskonen
Jarkko
J
Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0130, USA. jhuu6676@itsa.ucsf.edu
Abedin
Monika
M
Vishnu
Meeta
M
Pullinger
Clive R
CR
Baranzini
Sergio E
SE
Kane
John P
JP
Fielding
Phoebe E
PE
Fielding
Christopher J
CJ
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
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