Tuesday, November 29, 2005

Homologous Block Structure in the Promoter Regions

Comparative sequence analysis was carried out for the regions adjacent (1kb) to experimentally validated transcriptional start sites (TSSs), using 3324 pairs of human and mouse genes. Within the homologous blocks, the sequence identity was uniformly 65% regardless of their length. About 90% of the previously characterized transcription factor binding sites were located within those blocks. In 46% of the blocks, the 5' ends were bounded by interspersed repetitive elements, some of which may have nucleated the genomic rearrangements. The length of the blocks was shortest in the promoters of genes encoding transcription factors and of genes whose expression patterns are brain specific, which suggests that the evolutional diversifications in the transcriptional modulations should be the most marked in these populations of genes. [PMID: 15342556]

Wednesday, November 23, 2005

How to deal with the high false positive of computational putative TFBSs?

1. conservation between species.
2. take in account the combination of TFs[PMID: 11544200, PMID: 11752406].

Sunday, November 20, 2005

Examples that microRNA regulate the non-regulatory genes

The predicted targets of miR-277 in Drosophila include a striking enrichment of genes in the biochemical pathway for the catabolism of leucine, isoleucine and valine[PMID: 14691535]

Questions about microRNA

The function of microRNA, the evolution path of microRNA.

1. Prediction of the targets of microRNA.
2. How is the expression of microRNA regulated? [PMID: 15610730]
3. How do the mutliple-microRNAs play a role synergically?
4. The relationship among the functions of targets of single micorRNA.
5. How do the microRNA and transcription factor work together? [PMID: 15337119] Note: microRNA is definitely regulated by TFs.

Saturday, November 19, 2005

RNAi on or off target?

From: News and Views, Nature Genetics 34, 133 (2003)

Two new reports examine the specificity of RNA interference (RNAi) in human cells using genome-wide expression profiling. Targeting exogenous GFP in human embryonic kidney cells, Jen-Tsan Chi and colleagues report efficient and specific knockdown using two different siRNAs (Proc. Natl. Acad. Sci USA 10.1073/pnas.1037853100). Analysis of approximately 20,000 genes identified no consistent gene expression profile and no statistically significant difference in global gene expression patterns associated with the two siRNAs. Further analyses did not identify spreading of the RNAi effect to similar exogenous sequences, leading the authors to conclude that the RNAi effect is on target in mammalian cells. In a related paper, Peter Linsley and colleagues targeted endogenous genes (Nat. Biotechnol. 10.1038/nbt831). They examined the effect of 16 different siRNAs against IGF1R and 8 different siRNAs targeted against MAPK14. In each case, the gene expression profile was siRNA-specific. A group of 9 genes with partial sequence identity to the siRNA duplex targeted against MAPK14 were downregulated with similar kinetics. The authors conclude that at least some cross-hybridization of siRNAs to transcripts of similar sequences occurs. These results suggest that ensuring siRNA-specific effects requires well controlled experiments.

Thursday, November 10, 2005

the role of alternative promoters in mammalian genomes

In [PMID: 14585616], the authors estimated 18% of all human genes (~2500 loci) have evidence for alternative promoter usage. They also listed recently published studies of genes with alternative promoters.

The paper mentioned many interested feature regarding promoters:
1. Indeed, the use of endogenous retroviral sequences and other transposable elements as transcriptional promoters, although often over looked, is not uncommon in the genome.

2. The simplest and most common scenario involves two or more promoters that produce transcripts with identical ORFs. From studies published to date, it appears that 60–80% of genes with alternative promoters are of this type.

3. Does alternative promoter simply represent an inherent ‘leakiness’ in transcriptional control of the genome? Perhaps the strongest evidence supporting the idea that complex control of genes is not simply a biological artifact is the extent to which complex promoter structures are conserved between species. The examples of homologous genes with multiple promoters that are conserved in humans and rodents suggests that, in many cases, selective pressure has acted to maintain this complex regulation of gene expression.