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PMID:19632181

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Citation

Grove, CA, De Masi, F, Barrasa, MI, Newburger, DE, Alkema, MJ, Bulyk, ML and Walhout, AJ (2009) A multiparameter network reveals extensive divergence between C. elegans bHLH transcription factors. Cell 138:314-27

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.

Links

PubMed PMC2774807 Online version:10.1016/j.cell.2009.04.058

Keywords

Animals; Animals, Genetically Modified; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/metabolism; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; DNA/metabolism; Gene Regulatory Networks; Male; Molecular Sequence Data; Promoter Regions, Genetic; Protein Multimerization

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:G5EEG9

part_of

GO:0090575: RNA polymerase II transcription regulator complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P34555

C

Seeded From UniProt

complete

CAEEL:G5EEG9

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:G5EEG9

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00001959

F

Seeded From UniProt

complete

CAEEL:G5EEG9

enables

GO:0043425: bHLH transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P34555

F

Seeded From UniProt

complete

CAEEL:G5EEG9

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:G5EEG9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q23579

F

Seeded From UniProt

complete

CAEEL:MXL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:G5EG44

F

Seeded From UniProt

complete

CAEEL:G5EFA5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O02219

F

Seeded From UniProt

complete

CAEEL:MDL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:G5EEH5

F

Seeded From UniProt

complete

CAEEL:HIF1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O02219

F

Seeded From UniProt

complete

CAEEL:HIF1

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:HIF1

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00000095

F

Seeded From UniProt

complete

CAEEL:HIF1

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:HLH30

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:AHA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:G5EFA5

F

Seeded From UniProt

complete

CAEEL:AHA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:G5EGD2

F

Seeded From UniProt

complete

CAEEL:AHA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O44712

F

Seeded From UniProt

complete

CAEEL:AHA1

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:AHA1

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00001851

F

Seeded From UniProt

complete

CAEEL:AHA1

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00000096

F

Seeded From UniProt

complete

CAEEL:AHA1

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:AHR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O02219

F

Seeded From UniProt

complete

CAEEL:AHR

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00000095

F

Seeded From UniProt

complete

CAEEL:MYOD1

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:MYOD1

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:HLH4

part_of

GO:0090575: RNA polymerase II transcription regulator complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:G5EEG9

C

Seeded From UniProt

complete

CAEEL:HLH4

located_in

GO:0005634: nucleus

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P22980

C

Seeded From UniProt

complete

CAEEL:HLH4

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:HLH4

enables

GO:0043425: bHLH transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:G5EEG9

F

Seeded From UniProt

complete

CAEEL:HLH4

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:WBS14

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9TZ70

F

Seeded From UniProt

complete

CAEEL:HLH15

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00001949

F

Seeded From UniProt

complete

CAEEL:MXL3

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:MXL3

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:Q23579

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:Q23579

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:Q23579

enables

GO:0046982: protein heterodimerization activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:G5EEG9

F

Seeded From UniProt

complete

CAEEL:Q9TZ70

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P41846

F

Seeded From UniProt

complete

CAEEL:Q9XX00

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:Q9XX00

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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