| Abstract |
Διατμηματικό, συνεργαζόμενα Τμήματα Βιολογίας και Ιατρικής του Πανεπιστημίου Κρήτης. Low levels of high density lipoprotein (HDL) cholesterol constitute a risk factor for coronary heart disease, while there is evidence that raising HDL levels reduces the risk for cardiovascular disease independently of the levels of LDL. So, the effort to increase the levels of plasma HDL has become the focus of the HDL research. The ABCA1 transporter mediates cholesterol and phospholipid efflux to lipid-poor apolipoproteins and thus, it plays an important role in the regulation of plasma HDL. Mutations of the ABCA1 gene were identified in patients with Tangier disease, a condition characterized by very low levels of plasma HDL and an increased risk for premature coronary heart disease. The three different classes of ABCA1 transcripts are under the control of different promoter sequences. Class 3 transcripts originate in the sequence of intron 1 and they are the most abundant in liver. In the experiments described in this report, we used constructs containing deletions of an 8kb sequence upstream of exon 2 of the ABCA1 gene. The results suggest that the SREBP-1 transcription factor is capable of activating the transcription of these constructs in HepG2 cells. Two possible SREBP-1 binding sites in the sequence downstream of -167 are probably the cause of this activation. Moreover, there is evidence that intron 1 sequence is upregulated by the nuclear receptor RXR during stimulation by 9-cis retinoic acid. Even though these preliminary results require further investigation, they do provide significant evidence concerning the regulation of the promoter sequence in intron 1.
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Μεταγραφική ρύθμιση του γονιδίου ABCA1 στην περιοχή του ιντρονίου 1
