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We have identified the regulatory elements, some of the factors and potential regulatory mechanisms which determine the tissue specificity of the human apoC-II gene. The ؊545/؉18 apoC-II promoter directs high levels of expression of the reporter CAT gene in cells of hepatic origin (HepG2), low levels of expression in cells of intestinal origin (CaCo-2) and basal expression in HeLa cells. Deletion analysis identified negative regulatory elements within the ؊545/؊388 region and positive regulatory elements within the ؊388/؊55 region. Linkage of different apoC-II promoter segments to the hepatic control region-1 (HCR-1) enhanced the promoter activity 2.5-11-fold in HepG2 cells but did not affect its activity in CaCo-2 or COS-1 cells. DNase I footprinting analysis using rat liver nuclear extracts identified five protected regions within the ؊545/؉18 apoC-II promoter as follows: CIIA (؊74/؊44), CIIB (؊102/؊81), CIIC (؊159/؊116), CIID (؊288/؊265), and CIIE (؊497/؊462). Elements CIIB and CIIC contain hormone response elements. CIIB is recognized by hepatic nuclear factor-4 (HNF-4) but not ARP-1 or EAR-2, whereas CIIC is recognized by ARP-1 and EAR-2 but not by HNF-4. HNF-4 transactivated the apoC-II promoter or the apoC-II promoter linked to the HCR-1 in COS-1 cells. A double mutation in elements CIIB and CIIC that eliminated binding of HNF-4 or ARP-1 and EAR-2, respectively, to these sites abolished the enhancer activity of HCR-1. The combined data suggest that the apoC-II promoter/HCR-1 cluster can direct expression in cells of hepatic origin and that optimal enhancer activity requires synergistic interactions between factors bound to the distal HCR-1 and nuclear receptors bound to the two proximal hormone response elements. Plasma apolipoprotein CII (apoC-II)1 is a 79-amino acid protein that plays an important role in the catabolism of triglyceride-rich lipoproteins (1, 2). ApoC-II is a potent activator of the lipoprotein lipase, the enzyme that hydrolyzes the triglycerides of chylomicrons and very low density lipoproteins (3, 4). Patients with inherited apoC-II deficiency are unable to clear triglyceride-rich lipoprotein particles from their plasma, and develop type I hyperlipidemia (2, 5, 6). The human apoC-II gene has been mapped on the long arm of chromosome 19 in a gene cluster that contains the apoE/CI/CIЈ/CIV/CII genes and spans 45 kb of chromosomal region (7-9). The intergenic region between the apoC-II and apoC-IV genes is only 0.55 kb (1). The major site of apoC-II mRNA and protein synthesis in mammalian species is the liver and a minor site is the intestine (10 -12). Studies using transgenic mice have provided evidence for the existence of common regulatory regions within the 45 kb that control the tissue-specific expression of the apoC-I and apoE genes (13-15). These regions were designated hepatic control region-1 and -2 (HCR-1 and HCR-2), respectively (13,14).The objective of the current study was to identify the promoter elements which confer tissue specificity and assess the potential role of HCR-1 i...

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Human cord blood has been successfully used as an alternative source of hematopoietic stem cells suitable for transplantation. The aim of this study was to assess the impact of gestational age and the mode of delivery on cord blood hematopoietic stem/progenitor cell characteristics. The mode of delivery does not seem to affect either the replating capacity of hematopoietic progenitors colony-forming unit-granulocyte-macrophage or the cord blood content in CD34(+) cells. The higher percentage of CD34(+) cells in cord blood from preterm deliveries compared to full-term ones indicates that hematopoietic progenitors from preterm cord blood may be suitable for transplantation. These findings should be taken into consideration when selection of cord blood units is required for potential use in transplantation.