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. 2013 Dec 27;9(20):1010-2.
doi: 10.6026/97320630091010. eCollection 2013.

Genetic Variant of C-5312T Can Change Binding Pattern of Sp1 to Renin Enhancer that are Very Likely to Affect Renin Gene Expression

Mifetika Lukitasari  1 , Jayarani F Putri  2 , Muladefi Choiriyah  1 , Mohammad Saifur Rohman  3 , Nashi Widodo  2
Affiliations

Genetic Variant of C-5312T Can Change Binding Pattern of Sp1 to Renin Enhancer that are Very Likely to Affect Renin Gene Expression

Mifetika Lukitasari et al. Bioinformation. .

Abstract

Renin distal enhancer plays a pivotal role in renin gene expression, and the genetic variants C-5312T of renin enhancer can affect renin gene transcription level. However, the mechanism associated with the transcription level changes remains unknown. Therefore, it is of interest to investigate the possible role of distal enhancer in regulating the expression of renin gene. Single nucleotide polymorphism in renin distal enhancer was identified in 34 hypertensive patients by automatic sequencing. The data showed that the renin enhancer from the patients have genetic variants C-5312T or C-5312T SNP. Hence, the functionality of the renin enhancer and influence of the genetic variants C-5312T on binding to Sp1 is studied. These results from the binding study suggested that Sp1 binds to the DNA in GC rich region. Thus, the genetic variant C-5312T has changed the binding pattern of Sp1 to renin enhancer. This is likely to influence Sp1 activity to stimulate the expression of renin gene. The binding of Sp1 to the cis-element will enhance transcription of renin gene. Thus, polymorphism within C-5312T might contribute to the reduction of renin transcription.

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Figures

Figure 1
Figure 1
Genetic variation of Sp1-binding site at hypertensive patients. Consensus of Sp1-binding site was retrieved from Jaspar CORE database (A), Varian renin enhancer at -5312C (B), and variants of the renin enhancer at -5312T (C).
Figure 2
Figure 2
Complex molecules of 17β-Estradiol (cyan), ER (ed), Sp1 (blue) and the Renin Enhancer (gray) was resulted from docking analysis by using Escher NG in VEGAZZ. The presence of SNP in C-5312T has led to change the bonding pattern of Sp1 to renin enhancer. Sp1 bound to the major groove side of renin enhancer on-5312T (A), shifts to the minor grove on-5312C (B).
Figure 3
Figure 3
Binding pattern of Zinc Finger Domain of Sp1 (Pink) to renin enhancher (Grey) was identified by docking analysis using Hex 8, position of SNPs in C-5312T is shown in green (Left Panel). Interaction of Sp1 amino acids and DNA is indicated by arrows (Right Panel). Binding pattern of Zinc Finger Domain shifted from the middle of Sp1-binding site on - 5312T (A), to downstream of Sp1-binding site on -5312C (B).
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