A multiparameter network reveals extensive divergence between C. elegans bHLH transcription factors.
Differences in expression, protein interactions, and DNA binding of paralogous transcription factors ("TF parameters") are thought to be important determinants of regulatory and biological specificity. However, both the extent of TF divergence and the relative contribution of individual TF parameters remain undetermined. We comprehensively identify dimerization partners, spatiotemporal expression patterns, and DNA-binding specificities for the C. elegans bHLH family of TFs, and model these data into an integrated network. This network displays both specificity and promiscuity, as some bHLH proteins, DNA sequences, and tissues are highly connected, whereas others are not. By comparing all bHLH TFs, we find extensive divergence and that all three parameters contribute equally to bHLH divergence. Our approach provides a framework for examining divergence for other protein families in C. elegans and in other complex multicellular organisms, including humans. Cross-species comparisons of integrated networks may provide further insights into molecular features underlying protein family evolution. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.
Grove
Christian A
CA
Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
De Masi
Federico
F
Barrasa
M Inmaculada
MI
Newburger
Daniel E
DE
Alkema
Mark J
MJ
Bulyk
Martha L
ML
Walhout
Albertha J M
AJ
D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D053263:Gene Regulatory Networks; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D055503:Protein Multimerization
D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D004247:DNA