How could a SNP within a gene promoter alter gene expression levels? Promoter region SNPs affect the initiation and regulation of gene expression by altering the promoter activity, transcription factor binding, and altering DNA methylation, and histone modifications. They alter gene expression by affecting the binding site sequences.
SNPs are single nucleotide substitutions that occur in germline cells. When they occur in a gene promoter, the levels of gene expression can alter.
Key Areas Covered
1. What is an SNP
– Definition, Features, Importance
2. What is a Promoter
– Definition, Features, Importance
3. How Could an SNP Within a Gene Promoter Alter Gene Expression Levels
What is an SNP
SNP or single nucleotide polymorphism is one nucleotide substitution of the germline cells. A large fraction of the population should have a single nucleotide variation in order to become a single nucleotide polymorphism. Usually, 1% of the population needs to have the variation. For instance, a specific base position of the genome contains a G nucleotide. But the minority of individuals may have the nucleotide A. Therefore, the two possible variations of the nucleotide position are G and A.
Furthermore, SNP occurs in the germline cells. The main importance of SNP is that it makes individuals susceptible to diseases. Some examples of such a disease are age-related macular degeneration. Generally, a common SNP in the CFH gene increases the risk of the disease. Another example of SNP-related disease is nonalcoholic fatty liver disease. It occurs due to the presence of an SNP in the PNPLA3 gene in the genome.
What is a Promoter
A promoter is one of the main regulatory elements of the gene that initiates transcription. It is located near the gene, upstream of the codon sequence. The size of the promoter can be 100-1000 bp. The specific DNA sequences called response elements provide initial binding sites for both RNA polymerase and transcription factors which recruit RNA polymerase. RNA polymerase is the enzyme responsible for the transcription, polymerizing complementary RNA nucleotides to synthesize an mRNA molecule.
Moreover, bacterial RNA polymerase associated with the sigma factor can bind to the promoter. The sigma factor is a bacterial transcription initiation factor. In eukaryotes, around 7 different basal transcription factors have to be bound to the promoter to recruit RNA polymerase.
How Could an SNP Within a Gene Promoter Alter Gene Expression Levels
An SNP within a gene promoter alters the levels of gene expression. It can alter the gene expression by means of affecting the binding site sequences. This can occur in many ways. They include;
- altering the promoter activity,
- altering the transcription factor binding, and
- altering the DNA methylation and histone modifications.
SNPs also occur more prominently in transcriptional start sites in close proximity. Predicted SNPs occur in transcription factor binding sites.
Further, promoters occur in the regulatory region of the functionally important genes. They are also involved in the initiation and regulation of gene expression by binding specific transcription factors. The identification and binding of these transcription factors can alter in the presence of SNPs in the promoter region. It can affect the initiation of the gene expression. For example, SNP falling in the binding site of the interferon response factor-1 (IRF – 1) of the HLA-G gene affects the binding of IRF-1 to the gene, downregulating the transcription of the HLA-G gene.
In addition to that, altering the promoter region alters the promoter activity by SNPs affecting the levels of gene expression as promoter affects the regulation of gene expression. Other alterations in the DNA methylation and histone modifications can change the initiation and regulation of gene expression as well.
In brief, SNPs are single nucleotide substitutions occurring in the genes of the human genome. A promoter, on the other hand, is the regulatory region of the gene expression. It also binds to transcription factors during the initiation and the regulation of gene expression. Sometimes, SNPs can occur in the promoter region. This affects the identification and binding of transcription factors to the promoter region. In addition, it affects the DNA methylation and histone modifications of the promoter region. It also affects the activity of the promoter. Therefore, SNPs in the promoter region affect the levels of gene expression by altering the initiation and regulation of gene expression.
- Guo Y, Jamison DC. The distribution of SNPs in human gene regulatory regions. BMC Genomics. 2005 Oct 6;6:140. doi: 10.1186/1471-2164-6-140. PMID: 16209714; PMCID: PMC1260019.