Genomic structure of ATF5 regulatory region and polymorphism-related function. (A) Genomic structure of 2 ATF5 regions used in the luciferase assay. Exonic and coding sequences are represented by open and gray boxes, respectively, and SNPs are represented by gray dots. Alternatively spliced 5′UTRα and 5′UTRβ, as determined by Watatani et al,32 are indicated by the dark gray and black boxes, respectively. Note that 2 SNPs in LD, C-514T and A321T SNPs, which defines haplotype *3, are present in the first and the second fragment, respectively; 2 other SNPs in LD (C-270A/C1562T), which define haplotype *5, are both present in fragment 2. The black and gray arrows indicate the transcription and translation start sites, respectively, estimated according to Wei et al23 and Watatani et al32 and reference sequence NM012068. (B) Relative promoter activity of ATF5 haplotype *1,*2,*3, and *4 derived from fragment 1 (top panel) and haplotypes*2,*3, and *5 derived from fragment 2 (bottom panel) in 3 cell lines (HeLa, Jeg3, and HepG2). The haplotype numbers correspond to the haplotypes of the proximal promoter and 5′UTR given in Figure 1A. The haplotypes *1, *2, *3, *4, and *5 are defined by A-1072, G-34, T-514 (or T321 in correlation), C-670, and T1562 (or A-270 in correlation), respectively. Haplotypes showing a significant increase in promoter activity (P ≤ .02, ANOVA posthoc) compared with low-expression haplotypes are indicated by asterisks. (C) Relative mRNA levels in HapMap lymphoblastoid cell lines for individuals who are carriers or not of indicated alleles of ATF5 polymorphisms, which are defining haplotypes *1 to *5, respectively. Mean values ± SE are given. The number of individuals represented by each bar and the P value obtained by the Mann-Whitney test are indicated on the plots.
