Statistical analysis of combinatorial transcriptional regulatory motifs in human intron-containing promoter sequences

The combinatorial regulation is an important feature of transcriptional regulation of genes. Although a number of researches have been done, the general properties of combinatorial transcriptional regulatory elements, including their patterns and distributions, are still not well understood. Specially, the understanding for laws of transcriptional regulation involving introns is challenging. Here, we performed statistical analyses on potentially interacting motif pairs in human housekeeping genes and tissue-specific genes of some tissues. We first identified transcriptional regulatory motifs in promoter sequences, including the first introns, using a sequence-based approach which incorporates several different sequence backgrounds. And then we predicted the potentially interacting motif pairs using Hypergeometric distribution and Mann–Whitney U-test. The validation of the predicted interacting motif pairs has been carried out via analyses of orthologous conservation and enrichment. The distribution characteristics of the identified motif pairs were examined using a probability model. We found that interacting motif pairs have some significant preferences in location, distance and orientation in housekeeping and tissue-specific genes. The results suggest that the features of transcriptional regulation in housekeeping genes are different from the tissue-specific genes. Besides, location preferences of the motif pairs provide clues to the way of the introns participating in transcriptional regulation in different tissue-specific genes.

Graphical abstractLocation distributions of over-represented motif pairs in human tissues. (A) Six possible locations of a motif pair. (a) Both motifs are located in upstream region; (b) one is located in upstream region and another is in exon; (c) one is in upstream region and another is in intron; (d) both motifs are in exon; (e) one is in exon and another is in intron; and (f) both motifs are in intron. (B) The frequencies of motif pairs which prefer different numbers (0–4) of locations and (C) The frequencies of motif pairs prefer different locations.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We performed statistical analyses on potentially interacting motif pairs in human housekeeping genes and tissue-specific genes of some tissues. ► The distribution characteristics of the identified motif pairs were examined using a probability model. ► The results provide clues to the way of the introns participating in transcriptional regulation in different tissue-specific genes.