The CBS −4673 G allele attenuates transcription factor binding affinity.
(A) SPR analysis comparing the binding affinity of nuclear extracts to DNA
probes containing either the −4673 C or G alleles. The SPR-binding activity of the
A-allele (|logKD| = 9.75 ± 0.65) was more than 1 000-fold higher
than that of the C-allele (|logKD| = 6.12 ± 0.05). Each value
represents the mean ± SD of three experiments. (B) Competition SPR assays
performed in the presence of 5-fold excess non-biotinylated C- or G-allele probes.
(C) ChIP assays using HEK293 and cardiovascular tissue samples. The presence of
the SP1-binding CBS promoter was verified by PCR. (D) A luciferase
construct containing either the C or G allele was co-transfected with pcDNA3.1 (control)
or pcDNA3.1-SP1 expression plasmids. The actual values in HEK293 cells were as follows:
pcDNA3.1-basic group: pGL3-basic = 0.34 ± 0.08, pGL3-C allele = 2.27 ±
0.16, and pGL3-G allele = 3.54 ± 0.23; pcDNA3.1-SP1 group: pGL3-basic = 0.43
± 0.13, pGL3-C allele = 1.46 ± 0.12, and pGL3-G allele = 3.10 ±
0.16. The actual values in H9C2 cells were the following: pcDNA3.1 group: pGL3-basic =
0.31 ± 0.08, pGL3-C allele = 1.73 ± 0.14, and pGL3-G allele = 2.74
± 0.10; pcDNA3.1-SP1 group: pGL3-basic = 0.27 ± 0.03, pGL3-C allele = 1.14
± 0.12, and pGL3-G allele = 2.21 ± 0.18. Each value represented mean
± SD of three experiments, and each experiment was performed in triplicate.