by Patricia Babin
In this series, we’ve been discussing the use of so-called “junk” DNA—specifically Alu elements—as an argument for evolution. In part 1, I explained why evolutionists might believe that junk DNA is a sound argument and gave an overview of where we would be going in this series. In part 2, I covered the structure of a typical Alu element, the structural motifs present in Alu elements, and the location of these elements throughout the human genome. Part 3 examined Alu element functions related to their high copy number in the genome. Today, we’ll review the recent scientific data concerning the binding of transcription factors to Alu elements.
Binding Sites for Specific Transcription Factors
Without transcription factors, DNA would sit inert in the nucleus of the cell. There are two types of transcription factors responsible for orchestrating the transcription of RNA from DNA:
- General transcription factors
- Specific transcription factors
The ever-present general transcription factors are essential to the transcription of any gene that codes for a protein. Specific transcription factors are specific to individual genes (or sets of genes) and are responsive to varying conditions in the cell. Transcription factors differ from other molecules that affect DNA transcription (such as corepressors or coactivatorsin that they bind directly to a region of DNA near the gene they are regulating. For the remainder of this article, we’ll use the term “transcription factor” to mean “specific transcription factor.”
As discussed in part 3, researchers Paz Polak and Eytan Domany1 identified 66 unique transcription factors that have binding sites within Alu elements. The most prominent of these is p53. According to the study, Alu elements are enriched in biosynthesis genes and are sparser in genes that regulate embryogenesis. Interestingly, these scientists discovered that there are binding sites for embryogenesis-regulating transcription factors in Alu elements that are located near biosynthesis genes. The authors hypothesized that biosynthesis has to be down-throttled in order for energy and cellular components to be diverted to development. This balance, they theorize, is achieved by means of the binding of developmental transcription factors to Alu elements near biosynthesis genes.
Figure 1. Grey double helical structure running horizontally is Alu element DNA. There are four p53 molecules bound to the Alu element (blue, orange, green, and pink cylinders and ribbons). The binding motif for p53 (RRRCWWGYYY) is shown below the figure. R = ‘A’ or ‘G’, C = ‘C’, W = ‘A’ or ‘T’, G = ‘G’ and Y = ‘C’ or ‘T’. Image credit: Feng Cui, M. V. Sirotin, and V. B. Zhurkin, “Impact of Alu Repeats on the Evolution of Human p53 Binding Sites,” Biology Direct 6 (2011): 2–20.
While Alu elements constitute approximately 10 percent of the human genome, they are not distributed evenly throughout the genome. From 0 to 600 base pairs from the start of genes, Alu elements constitute less than 10 percent of the genome. The density of Alu elements increases as you move past 600 base pairs and reaches a maximum density of 18 percent at 2,000 base pairs from the start of genes. After this point, the density gradually decreases to less than 10 percent. Eighty-five percent of the genes in the database used for Polak and Domany’s study have at least one Alu element within 5,000 base pairs from the start of the gene. This non-random distribution is in keeping with the numerous and important roles of Alu elements in the genome, especially with regard to regulation of transcription through the binding of transcription factors.
The binding sites cited in this study range from 7 to 18 base pairs in length. Since an Alu element is only 300 base pairs long and binding sites for 66 transcription factors need to be accounted for within the 300 base pairs, it is evident that the binding sites must overlap one another. It would never be possible for more than a few transcription factors to bind to an individual element at any moment in time. This necessity highlights another important aspect of Alu element functionality. Since there are so many Alu elements in a cell with a wide variety of functions, each of them must function appropriately based its location. For example, an individual transcription factor must bind to a specific Alu element based on the proximity of that Alu element to the gene that the transcription factor regulates. For 29 out of the 66 transcription factors identified in this study, the majority of their binding sites in the genome were located on Alu elements. Several transcription factors bind almost exclusively to sequences found within Alu elements.
There remains much work to be done in understanding the function of many of these transcription factors in binding to Alu elements. However, the biological function of a subset of them has already been demonstrated in vivo.2 The biological processes affected by transcription factor binding to Alu elements include:
- heart development
- muscle development
- stress response
- brain development
- central nervous system development
- pancreas development
Though we’ve focused strictly on Alu elements’ role in binding transcription factors, these elements possess other functions that demonstrate just how exquisitely they are designed. Next week we’ll explore four additional functions of Alu elements.
|Part 1 | Part 2 | Part 3 | Part 4 | Part 5 | Part 6|
- Paz Polak and Eytan Domany, “Alu Elements Contain Many Binding Sites for Transcription Factors and May Play a Role in Regulation of Developmental Processes,” BMC Genomics 2006, 7 (2006): 133–47