Transcription factor binding to Caenorhabditis elegans first introns reveals lack of redundancy with gene promoters.
Gene expression is controlled through the binding of transcription factors (TFs) to regulatory genomic regions. First introns are longer than other introns in multiple eukaryotic species and are under selective constraint. Here we explore the importance of first introns in TF binding in the nematode Caenorhabditis elegans by combining computational predictions and experimentally derived TF-DNA interaction data. We found that first introns of C. elegans genes, particularly those for families enriched in long first introns, are more conserved in length, have more conserved predicted TF interactions and are bound by more TFs than other introns. We detected a significant positive correlation between first intron size and the number of TF interactions obtained from chromatin immunoprecipitation assays or determined by yeast one-hybrid assays. TFs that bind first introns are largely different from those binding promoters, suggesting that the different interactions are complementary rather than redundant. By combining first intron and promoter interactions, we found that genes that share a large fraction of TF interactions are more likely to be co-expressed than when only TF interactions with promoters are considered. Altogether, our data suggest that C. elegans gene regulation may be additive through the combined effects of multiple regulatory regions.
Program in Systems Biology, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA, Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA and Divisions of Rheumatology and Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Juan I
JI
Fuxman Bass
Alex M
AM
Tamburino
Akihiro
A
Mori
Nathan
N
Beittel
Matthew T
MT
Weirauch
John S
JS
Reece-Hoyes
Albertha J M
AJ
Walhout
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D007438:Introns; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*
D014157:Transcription Factors