Correlating disordered activation domain ensembles with gene expression levels
Transcription factor proteins bind to specific DNA promoter sequences and initiate gene transcription. These proteins often contain intrinsically disordered activation domains (ADs) that regulate their transcriptional activity. Like other disordered protein regions, ADs do not have a fixed three-dim...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Biophysical Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667074724000545 |
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| author | Eduardo Flores Aleah R. Camacho Estefania Cuevas-Zepeda Mary B. McCoy Feng Yu Max V. Staller Shahar Sukenik |
| author_facet | Eduardo Flores Aleah R. Camacho Estefania Cuevas-Zepeda Mary B. McCoy Feng Yu Max V. Staller Shahar Sukenik |
| author_sort | Eduardo Flores |
| collection | DOAJ |
| description | Transcription factor proteins bind to specific DNA promoter sequences and initiate gene transcription. These proteins often contain intrinsically disordered activation domains (ADs) that regulate their transcriptional activity. Like other disordered protein regions, ADs do not have a fixed three-dimensional structure and instead exist in an ensemble of conformations. Disordered ensembles contain sequence-encoded structural preferences that are often linked to their function. We hypothesize that this link exists between the structural preferences of AD ensembles and their ability to induce gene expression. To test this, we measured the ensemble dimensions of two ADs, HIF-1α and CITED2, in live cells using fluorescence resonance energy transfer microscopy and correlated this structural information with their transcriptional activity. We find that mutations that expanded the ensemble of HIF-1α increased transcriptional activity, while compacting mutations reduced it, highlighting the critical role of structural plasticity in regulating HIF-1α function. Conversely, CITED2 showed no correlation between ensemble dimensions and activity. Our results highlight a possible link between AD ensemble dimensions and their transcriptional activity, with implications for transcriptional regulation and dysfunction. |
| format | Article |
| id | doaj-art-d9ea8745107043e3b1b5ac537d308cd7 |
| institution | Kabale University |
| issn | 2667-0747 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biophysical Reports |
| spelling | doaj-art-d9ea8745107043e3b1b5ac537d308cd72025-01-22T05:44:15ZengElsevierBiophysical Reports2667-07472025-03-0151100195Correlating disordered activation domain ensembles with gene expression levelsEduardo Flores0Aleah R. Camacho1Estefania Cuevas-Zepeda2Mary B. McCoy3Feng Yu4Max V. Staller5Shahar Sukenik6Department of Chemistry and Biochemistry, University of California, Merced, Merced, CaliforniaDepartment of Chemistry and Biochemistry, University of California, Merced, Merced, CaliforniaDepartment of Chemistry and Biochemistry, University of California, Merced, Merced, CaliforniaDepartment of Chemistry and Biochemistry, University of California, Merced, Merced, CaliforniaDepartment of Chemistry and Biochemistry, University of California, Merced, Merced, California; Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CaliforniaDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California; Center for Computational Biology, University of California, Berkeley, Berkeley, California; Chan Zuckerberg Biohub–San Francisco, San Francisco, CaliforniaDepartment of Chemistry and Biochemistry, University of California, Merced, Merced, California; Department of Chemistry, Syracuse University, Syracuse, New York; Corresponding authorTranscription factor proteins bind to specific DNA promoter sequences and initiate gene transcription. These proteins often contain intrinsically disordered activation domains (ADs) that regulate their transcriptional activity. Like other disordered protein regions, ADs do not have a fixed three-dimensional structure and instead exist in an ensemble of conformations. Disordered ensembles contain sequence-encoded structural preferences that are often linked to their function. We hypothesize that this link exists between the structural preferences of AD ensembles and their ability to induce gene expression. To test this, we measured the ensemble dimensions of two ADs, HIF-1α and CITED2, in live cells using fluorescence resonance energy transfer microscopy and correlated this structural information with their transcriptional activity. We find that mutations that expanded the ensemble of HIF-1α increased transcriptional activity, while compacting mutations reduced it, highlighting the critical role of structural plasticity in regulating HIF-1α function. Conversely, CITED2 showed no correlation between ensemble dimensions and activity. Our results highlight a possible link between AD ensemble dimensions and their transcriptional activity, with implications for transcriptional regulation and dysfunction.http://www.sciencedirect.com/science/article/pii/S2667074724000545 |
| spellingShingle | Eduardo Flores Aleah R. Camacho Estefania Cuevas-Zepeda Mary B. McCoy Feng Yu Max V. Staller Shahar Sukenik Correlating disordered activation domain ensembles with gene expression levels Biophysical Reports |
| title | Correlating disordered activation domain ensembles with gene expression levels |
| title_full | Correlating disordered activation domain ensembles with gene expression levels |
| title_fullStr | Correlating disordered activation domain ensembles with gene expression levels |
| title_full_unstemmed | Correlating disordered activation domain ensembles with gene expression levels |
| title_short | Correlating disordered activation domain ensembles with gene expression levels |
| title_sort | correlating disordered activation domain ensembles with gene expression levels |
| url | http://www.sciencedirect.com/science/article/pii/S2667074724000545 |
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