STRUCTURE OF THE HUMAN GENE ENCODING STEROL REGULATORY ELEMENT-BINDING PROTEIN-2 (SREBF2)

Sterol-regulatory element binding protein (SREBP) 1 and SREBP2 are ubi quitously expressed transcription factors that play key roles in the r egulation of cholesterol and fatty acid metabolism. SREBP1 and SREBP2 share similar to 47% sequence identity and map to chromosomes 17 and 2 2, respectively. The gene encoding SREBP1 (SREBF1) has been cloned and characterized. In this paper we describe the gene structure and 5'-fl anking sequence of SREBF2. SREBF2 spans 72 kb and is composed of 19 ex ons and 18 introns. The locations of the exon/intron boundaries of SRE BF2 are remarkably similar to those of SREBF1, but SREBF2 is approxima tely 2.8 times larger in size. The 5'-flanking regions of SREBF2 and o f two alternatively spliced forms of SREBF1, SREBF1a and SREBF1c, were sequenced, and the SREBF2 transcription start site was determined, A perfect 10-bp sterol regulatory element (SRE)-1 sequence was present i n the promoter region of SREBF2. No SRE-1 was identified in the 5'-fla nking sequences of either SREBF1a or SREBF1c, but several E-box sequen ces were present in SREBP1c. Thus, analysis of the 5'-flanking regions provides support that these two transcription factors, though similar in their coding sequence and overall gene structure, have different p hysiological roles, Finally, evidence is presented for the presence of another expressed gene of unknown function located 500 bp upstream of SREBF2. (C) 1997 Academic Press