START domains generate paralog-specific regulons from a single network architecture
Abstract Functional divergence of transcription factors (TFs) has driven cellular and organismal complexity throughout evolution, but its mechanistic drivers remain poorly understood. Here we test for new mechanisms using CORONA (CNA) and PHABULOSA (PHB), two functionally diverged paralogs in the CL...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54269-z |
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| author | Ashton S. Holub Sarah G. Choudury Ekaterina P. Andrianova Courtney E. Dresden Ricardo Urquidi Camacho Igor B. Zhulin Aman Y. Husbands |
| author_facet | Ashton S. Holub Sarah G. Choudury Ekaterina P. Andrianova Courtney E. Dresden Ricardo Urquidi Camacho Igor B. Zhulin Aman Y. Husbands |
| author_sort | Ashton S. Holub |
| collection | DOAJ |
| description | Abstract Functional divergence of transcription factors (TFs) has driven cellular and organismal complexity throughout evolution, but its mechanistic drivers remain poorly understood. Here we test for new mechanisms using CORONA (CNA) and PHABULOSA (PHB), two functionally diverged paralogs in the CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) family of TFs. We show that virtually all genes bound by PHB ( ~ 99%) are also bound by CNA, ruling out occupation of distinct sets of genes as a mechanism of functional divergence. Further, genes bound and regulated by both paralogs are almost always regulated in the same direction, ruling out opposite regulation of shared targets as a mechanistic driver. Functional divergence of CNA and PHB instead results from differential usage of shared binding sites, with hundreds of uniquely regulated genes emerging from a commonly bound genetic network. Regulation of a given gene by CNA or PHB is thus a function of whether a bound site is considered ‘responsive’ versus ‘non-responsive’ by each paralog. Discrimination between responsive and non-responsive sites is controlled, at least in part, by their lipid binding START domain. This suggests a model in which HD-ZIPIII TFs use information integrated by their START domain to generate paralog-specific transcriptional outcomes from a shared network architecture. Taken together, our study identifies a mechanism of HD-ZIPIII TF paralog divergence and proposes the ubiquitously distributed START evolutionary module as a driver of functional divergence. |
| format | Article |
| id | doaj-art-827857b1142b407a9c149a90e0c0d6ba |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-827857b1142b407a9c149a90e0c0d6ba2024-11-17T12:36:01ZengNature PortfolioNature Communications2041-17232024-11-0115111810.1038/s41467-024-54269-zSTART domains generate paralog-specific regulons from a single network architectureAshton S. Holub0Sarah G. Choudury1Ekaterina P. Andrianova2Courtney E. Dresden3Ricardo Urquidi Camacho4Igor B. Zhulin5Aman Y. Husbands6Department of Biology, University of PennsylvaniaDepartment of Biology, University of PennsylvaniaDepartment of Microbiology, The Ohio State UniversityDepartment of Biology, University of PennsylvaniaDepartment of Biology, University of PennsylvaniaDepartment of Microbiology, The Ohio State UniversityDepartment of Biology, University of PennsylvaniaAbstract Functional divergence of transcription factors (TFs) has driven cellular and organismal complexity throughout evolution, but its mechanistic drivers remain poorly understood. Here we test for new mechanisms using CORONA (CNA) and PHABULOSA (PHB), two functionally diverged paralogs in the CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) family of TFs. We show that virtually all genes bound by PHB ( ~ 99%) are also bound by CNA, ruling out occupation of distinct sets of genes as a mechanism of functional divergence. Further, genes bound and regulated by both paralogs are almost always regulated in the same direction, ruling out opposite regulation of shared targets as a mechanistic driver. Functional divergence of CNA and PHB instead results from differential usage of shared binding sites, with hundreds of uniquely regulated genes emerging from a commonly bound genetic network. Regulation of a given gene by CNA or PHB is thus a function of whether a bound site is considered ‘responsive’ versus ‘non-responsive’ by each paralog. Discrimination between responsive and non-responsive sites is controlled, at least in part, by their lipid binding START domain. This suggests a model in which HD-ZIPIII TFs use information integrated by their START domain to generate paralog-specific transcriptional outcomes from a shared network architecture. Taken together, our study identifies a mechanism of HD-ZIPIII TF paralog divergence and proposes the ubiquitously distributed START evolutionary module as a driver of functional divergence.https://doi.org/10.1038/s41467-024-54269-z |
| spellingShingle | Ashton S. Holub Sarah G. Choudury Ekaterina P. Andrianova Courtney E. Dresden Ricardo Urquidi Camacho Igor B. Zhulin Aman Y. Husbands START domains generate paralog-specific regulons from a single network architecture Nature Communications |
| title | START domains generate paralog-specific regulons from a single network architecture |
| title_full | START domains generate paralog-specific regulons from a single network architecture |
| title_fullStr | START domains generate paralog-specific regulons from a single network architecture |
| title_full_unstemmed | START domains generate paralog-specific regulons from a single network architecture |
| title_short | START domains generate paralog-specific regulons from a single network architecture |
| title_sort | start domains generate paralog specific regulons from a single network architecture |
| url | https://doi.org/10.1038/s41467-024-54269-z |
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