Promoter Structures Conserved between Homo Sapiens, Mus Musculus and Drosophila Melanogaster

Promoter Structures Conserved between Homo Sapiens, Mus Musculus and Drosophila Melanogaster

Boris R. Jankovic (King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia), John A. C. Archer (King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia), Rajesh Chowdhary (Biomedical Informatics Research Center, USA), Ulf Schaefer (King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia) and Vladimir B. Bajic (King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia)
DOI: 10.4018/978-1-61350-435-2.ch004
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Abstract

Some of the key processes in living organisms remain essentially unchanged even in evolutionarily very distant species. Transcriptional regulation is one such fundamental process that is essential for cell survival. Transcriptional control exerts great part of its effects at the level of transcription initiation mediated through protein-DNA interactions mainly at promoters but also at other control regions. In this chapter, the authors identify conserved families of motifs of promoter regulatory structures between Homo sapiens, Mus musculus and Drosophila melanogaster. By a promoter regulatory structure they consider here a combination of motifs from identified motif families. Conservation of promoter structure across these vertebrate and invertebrate genomes suggests the presence of a fundamental promoter architecture and provides the basis for deeper understanding of the necessary components of the transcription regulation machinery. The authors reveal the existence of families of DNA sequence motifs that are shared across all three species in upstream promoter regions. They further analyze the relevance of our findings for better understanding of preserved regulatory mechanisms and associated biology insights.
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Background

The three species in our study were chosen primarily because their genomic sequences and TSSs are well studied and documented in addition to their evolutionary relationship. We would expect that the number of shared MFs would decrease with evolutionary distance, but the nature and dynamics of this process is another interesting aspect of our study.

Studying of promoter motifs for D.melanogaster is reported in (Down et al., 2007). This study reveals through statistical analysis 87 novel motifs putatively involved in transcription factor binding. These motifs are determined using only fruit fly promoters and need not be conserved in evolutionary remote species. However, one can look at the shared MFs in promoter regions of several species. The basic idea is that presence of same MFs in promoter regions may suggest conserved regulatory functionality. Clearly, the number of shared MFs, together with the lengths of motifs implies statistical significance of any such commonality.

Organisms that are well studied as well as being evolutionary distant are particularly good candidates for such an analysis. Because it satisfies these requirements, the comparison between human and Fly promoters is particularly convenient. Because of these properties, this combination has been studied before (FitzGerald et al, 2006). That study evaluates conserved regions by detecting presence and frequencies of all possible octamers on close to 11,000 Fly promoters and two sets of human promoters, approximately 12,000 – 15,000 records. Their study finds that “Fly and human promoters use different DNA sequences to regulate gene expression, supporting the idea that evolution occurs by modulation of gene expression” (FitzGerald et al, 2006, page 1).

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