ical pathways, and at the same time, meet the demands of biochemical network dynamics. Gene expression carries expensive metabolic overhead. Signaling pathways are often used to regulate transcription factors to specify the genes for active transcription. A signaling step, usually a protein kinase, consumes an ATP molecule for protein phosphorylation. Upon initiation, the transcribing RNA polymerase consumes more ATP molecules and ribo-nucleotide building blocks to synthesize transcript product of the gene. Thus it is vital to utilize the signaling and the transcription machineries in the most economical manner, and to minimize un-necessary wasteful transcription events. For transcription regulation, genomic regulatory sequences play prominent roles in transcription regulation. Important signals embedded in the sequences include short motifs, to which transcription factors bind to activate or turn off transcription. Even though eukaryotic genes are independent transcriptional units, functionally related genes tend to have similar expression profiles. It is a general assumption that regulatory sequences of such genes embed similar profiles of transcription factor binding sites, often termed transcription factor binding site modules. Computational analysis of eukaryotic regulatory sequences, however, remains technically challenging; satisfactory predictive power remains elusive. Part of the blame might be low signal-to- noise ratio, as transcription factor binding sites are generally short and permutation tolerant. It might also be partially due to the fact that we have not understood eukaryotic transcription regulation well enough yet. Additionally, our finding suggests that using steady-state mRNA abundance data as input to such computa- tional analysis, as is generally practiced, might bear part of the blame as well. Transcription rate data, which is free from interference by mRNA degradation, should be a better input in regulatory sequence analysis. While our understanding of transcription regulation is far from satisfactory, we understand even less about mRNA degradation regulation. Much progress has been made, especially the recent discovery of miRNA mediated mRNA degradation mechanism [29]. Functionally related genes tend to have their mRNA products co-degraded, thus the term ‘‘degradation regulon’’ has been used to describe this phenomenon. But much of the cellular References 1. Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nature reviews 5: 101–113. 2. Davidson EH, Rast JP, Oliveri P, Ransick A, Calestani C, et al. (2002) A Genomic Regulatory Network for Development. Science 295: 1669– 1678. 3. 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