| We sought regulatory elements by shotgun cloning human exonic DNA fragments into luciferase reporter vectors and assessing transcriptional regulatory activity in liver cells. Seven elements within coding regions and three within 3' UTRs were discovered. Putative regulatory elements were generally but not consistently evolutionarily conserved, enriched in known transcription factor binding sites (TFBSs) and associated with several histone modifications. Evidence of cis-regulatory potential of an element within a TUBA1B exon was established by correlating expression of TUBA1B with activation of transcription factors predicted to have binding sites within this element. Nevertheless, no clear rules defining coding regulatory elements emerged. We estimate that hundreds of exonic regulatory elements exist, an unexpected finding that highlights a surprising multi-functionality of sequences in the human genome. |
