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A Multiparameter Network Reveals Extensive Divergence between C. elegans bHLH Transcription Factors

Authors: Grove, Christian A.; De Masi, Federico; Barrasa, M. Inmaculada; Newburger, Daniel E.; Alkema, Mark J; Bulyk, Martha L.; Walhout, Albertha J M;

A Multiparameter Network Reveals Extensive Divergence between C. elegans bHLH Transcription Factors

Abstract

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.

Country
United States
Keywords

Male, 570, SYSBIO, PROTEINS, Biochemistry, Genetics and Molecular Biology(all), Molecular Sequence Data, 500, Genetically Modified, Genetics and Genomics, DNA, Promoter Regions, Animals, Genetically Modified, Genetic, Basic Helix-Loop-Helix Transcription Factors, Animals, Gene Regulatory Networks, Protein Multimerization, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Promoter Regions, Genetic

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
237
Top 1%
Top 1%
Top 1%
hybrid