Motif Discovery in Promoters of Genes Co-Expressed and Co-Localized in Myelopoiesis...

...by a Novel Computational Framework
Alessandro Coppe
Morning Session 1 September (11th MGED Meeting, 1-4 September, 2008)

Genes similarly expressed and/or co-regulated may share common regulatory elements in their regulatory regions. Motifs recognized by a specific regulatory protein can differ slightly from one gene to another. They were investigating the role or promoter similarity and gene clustering in establishing co-expression of genes. They used hematopoiesis as a biological model for studying regulation of gene expression in cellular differentiation. In the starting dataset, there were 9716 genes for which genomic localization, promoter sequences, and expression data in myeloid cells were available. They then searched for CERs (co-expressed chromosomal regions), which are groups of adjacent genes co-expressed during myelopoiesis. They ended up with 26 CERs. 15 CERs were grouped into 2 co-expressed chromosomal meta-regions (CEMRs) by QT clustering.

Requirements of the custom motif discovery framework: finding motifs in a selected set of promoter sequences, not simply highly-over-represented with respect to random sequences. CEG, CER and CEMR are the groups of genes used for the motif discovery analysis. 5325 significantly over-represented motifs (FDR < 0.05) identified in 59 of the 72 considered groups of gene promoters. 19% of the motifs are similar to at least one of the 142 known TFBS. More common motifs were found in the promoters of co-localized and co-expressed genes than in those of simply co-expressed genes.

These are just my notes and are not guaranteed to be correct. Please feel free to let me know about any errors, which are all my fault and not the fault of the speaker. :)