Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction
Abstract Background The molecular function of a gene is most commonly inferred by sequence similarity. Therefore, genes that lack sufficient sequence similarity to characterized genes (such as certain classes of transcriptional regulators) are difficult to classify using most function prediction alg...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12864-017-3853-9 |
| _version_ | 1819078297678512128 |
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| author | Flavia Bossi Jue Fan Jun Xiao Lilyana Chandra Max Shen Yanniv Dorone Doris Wagner Seung Y. Rhee |
| author_facet | Flavia Bossi Jue Fan Jun Xiao Lilyana Chandra Max Shen Yanniv Dorone Doris Wagner Seung Y. Rhee |
| author_sort | Flavia Bossi |
| collection | DOAJ |
| description | Abstract Background The molecular function of a gene is most commonly inferred by sequence similarity. Therefore, genes that lack sufficient sequence similarity to characterized genes (such as certain classes of transcriptional regulators) are difficult to classify using most function prediction algorithms and have remained uncharacterized. Results To identify novel transcriptional regulators systematically, we used a feature-based pipeline to screen protein families of unknown function. This method predicted 43 transcriptional regulator families in Arabidopsis thaliana, 7 families in Drosophila melanogaster, and 9 families in Homo sapiens. Literature curation validated 12 of the predicted families to be involved in transcriptional regulation. We tested 33 out of the 195 Arabidopsis putative transcriptional regulators for their ability to activate transcription of a reporter gene in planta and found twelve coactivators, five of which had no prior literature support. To investigate mechanisms of action in which the predicted regulators might work, we looked for interactors of an Arabidopsis candidate that did not show transactivation activity in planta and found that it might work with other members of its own family and a subunit of the Polycomb Repressive Complex 2 to regulate transcription. Conclusions Our results demonstrate the feasibility of assigning molecular function to proteins of unknown function without depending on sequence similarity. In particular, we identified novel transcriptional regulators using biological features enriched in transcription factors. The predictions reported here should accelerate the characterization of novel regulators. |
| first_indexed | 2024-12-21T19:10:52Z |
| format | Article |
| id | doaj.art-f8130d61cf854c949074a21a4ea794e6 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-21T19:10:52Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-f8130d61cf854c949074a21a4ea794e62022-12-21T18:53:12ZengBMCBMC Genomics1471-21642017-06-0118112010.1186/s12864-017-3853-9Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent predictionFlavia Bossi0Jue Fan1Jun Xiao2Lilyana Chandra3Max Shen4Yanniv Dorone5Doris Wagner6Seung Y. Rhee7Department of Plant Biology, Carnegie Institution for ScienceDepartment of Plant Biology, Carnegie Institution for ScienceDepartment of Biology, University of PennsylvaniaDepartment of Plant Biology, Carnegie Institution for ScienceDepartment of Biology, University of PennsylvaniaDepartment of Plant Biology, Carnegie Institution for ScienceDepartment of Biology, University of PennsylvaniaDepartment of Plant Biology, Carnegie Institution for ScienceAbstract Background The molecular function of a gene is most commonly inferred by sequence similarity. Therefore, genes that lack sufficient sequence similarity to characterized genes (such as certain classes of transcriptional regulators) are difficult to classify using most function prediction algorithms and have remained uncharacterized. Results To identify novel transcriptional regulators systematically, we used a feature-based pipeline to screen protein families of unknown function. This method predicted 43 transcriptional regulator families in Arabidopsis thaliana, 7 families in Drosophila melanogaster, and 9 families in Homo sapiens. Literature curation validated 12 of the predicted families to be involved in transcriptional regulation. We tested 33 out of the 195 Arabidopsis putative transcriptional regulators for their ability to activate transcription of a reporter gene in planta and found twelve coactivators, five of which had no prior literature support. To investigate mechanisms of action in which the predicted regulators might work, we looked for interactors of an Arabidopsis candidate that did not show transactivation activity in planta and found that it might work with other members of its own family and a subunit of the Polycomb Repressive Complex 2 to regulate transcription. Conclusions Our results demonstrate the feasibility of assigning molecular function to proteins of unknown function without depending on sequence similarity. In particular, we identified novel transcriptional regulators using biological features enriched in transcription factors. The predictions reported here should accelerate the characterization of novel regulators.http://link.springer.com/article/10.1186/s12864-017-3853-9Genes with unknown functionTranscriptional regulatorsCoactivatorsPolycomb repressive complex 2 |
| spellingShingle | Flavia Bossi Jue Fan Jun Xiao Lilyana Chandra Max Shen Yanniv Dorone Doris Wagner Seung Y. Rhee Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction BMC Genomics Genes with unknown function Transcriptional regulators Coactivators Polycomb repressive complex 2 |
| title | Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction |
| title_full | Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction |
| title_fullStr | Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction |
| title_full_unstemmed | Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction |
| title_short | Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction |
| title_sort | systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction |
| topic | Genes with unknown function Transcriptional regulators Coactivators Polycomb repressive complex 2 |
| url | http://link.springer.com/article/10.1186/s12864-017-3853-9 |
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