There has been much evidence recently for a link between transcriptional regulation and chromosomal gene order, but the relationship between genomic organization, regulation and gene function in higher eukaryotes remains to be precisely defined. Analyzing the cardiac transcriptome identified by our genome-wide array analysis, FANTOM and GNF Symatlas data sets, we found striking evidence for such relationship. Highly co-expressed gene clusters are phylogenetically conserved, have a length limit and mainly consist of non-paralogous genes, and show a weaker functional and similar regulatory relationship to each other than general genomic neighbors. Thus, our data point to so far unknown cis-acting units and reject co-functionality as a driving force. We hypothesize that highly co-expressed gene clusters are essential for a higher order of transcriptional regulation, while specific transcription factors are likely to handle the fine-tuning of transcription on shorter time scales.
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Fig1: Distribution of shared tissue expression and features (TFBS, GO Terms, Protein Domains) for human chromosome 8. |