ATF3 rSNPs, transcriptional factor binding sites and human etiology.docVIP

Open Journal of Genetics, 2013, 3, 253-261 OJGen /10.4236/ojgen.2013.34028 Published Online December 2013 (/journal/ojgen/) ATF3 rSNPs, transcriptional factor binding sites and human etiology* Norman E. Buroker Department of Pediatrics, University of Washington, Seattle, USA Email: nburoker@ Received 26 September 2013; revised 25 October 2013; accepted 15 November 2013 Copyright ? 2013 Norman E. Buroker. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT transcription factor binding sites (TFBS). Single nucleotide changes that affect gene expression by impacting gene regulatory sequences such as promot- ers, enhancers, and silencers are known as regulatory SNPs (rSNPs) [7-10]. A rSNPs within a transcriptional factor binding site (TFBS) can change a transcriptional factor’s (TF) ability to bind its TFBS [11-14], in which case the TF would be unable to effectively regulate its target gene [15-19]. This concept is examined for the above ATF3 SNPs of intron one and their allelic associa- tion with TFBS. In this report, I discuss these SNP asso- ciations with changes in potential TFBS and their possi- ble relationship to human etiology. Three rSNPs (rs3125289, rs1877474 and r in one intron of the activating transcription factor 3 (ATF3) gene have been significantly associated with the human etiology of hypospadias and may be asso- ciated with human disease. These rSNP alleles alter the DNA landscape for potential transcriptional fac- tors (TFs) to attach resulting in changes in transcrip- tional factor binding sites (TFBS). These TFBS chan- ges are examined with respect to the human etiology of hypospadias which has been found to be signifi- cantly associated with the rSNPs. Keywords: ATF3; rSNPs; TFBS; Human Eti