Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
Sequence Studies of Promoter Regions in Human Genome
Recognition of promoter elements by the transcription factors is one of the initial and crucial steps in gene expression. In prokaryotes, there are clear signals to identify the promoter regions like TATAAT at -10 and TTGACA at -35 positions from transcription start site (TSS). However, in eukaryotes the promoter regions are structurally more complex and there are no conserved or consensus sequences similar to the ones found in prokaryotic promoters.
From sequence studies, we located a set of GC rich short sequences (>5 nt) that are relatively common in human promoter sequences around the TSS (±100 wrt TSS). These sequences were sorted based on their frequency and the top most common 50 sequences were used for further studies. The sigmoidal behvaior of the frequency distribution of these short sequences suggest presence of some internal co-operativity. These short sequences are distributed on both sides of TSS, suggesting that probably the transcription factors recognize these sequences on both upstream and downstream of TSS as an essential requirement during initial stages of the transcription. As eukaryotic promoters lack any conserved sequences, we expect that these short sequences may help in recognition of promoter regions by relevant transcription factors prior to the initiation of transcription process. Similarity, studies within these short sequences suggest that a set of sequences can be clustered together based on their match and mismatch score values. We suggest that a cluster of genes with common short sequences can be recognized by a perticular transcription factor. We also found that these short sequences occur within miRNA, both mature and stem-loop sequences. The distributions of the same set of short sequences within the miRNA dataset are under active investigation. We presume that miRNAs are playing some significant role in recognition of the promoter regions during initial stages of transcription, via the transcription factors. We have attempted to correlate the promoter sequences and miRNAs based on these common short sequences. We hope to show/establish a simple relation about the role of miRNA in recognition of promoter elements during initial stages of transcription.
Our studies indicate that eukaryotic transcription is more complex than currently believed. Further studies on promoter regions and transcription factors will bring new insights about the promoter architecture and complex events in transcriptional mechanism of eukaryotes. The short sequences present on both sides of the TSS, can be used as targets for gene therapy.