The molecular grammar of protein disorder guiding genome-binding locations

Intrinsically disordered regions (IDRs) direct transcription factors (TFs) towards selected genomic occurrences of their binding motif, as exemplified by budding yeast's Msn2. However, the sequence basis of IDR-directed TF binding selectivity remains unknown. To reveal this sequence grammar, we...

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Autores principales: Jonas, Felix, Carmi, Miri, Krupkin, Beniamin, Steinberger, Joseph, Brodsky, Sagie, Jana, Tamar, Barkai, Naama
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Gene regulation, Chromatin and Epigenetics
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10250222/
https://www.ncbi.nlm.nih.gov/pubmed/36938874
http://dx.doi.org/10.1093/nar/gkad184
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author Jonas, Felix
Carmi, Miri
Krupkin, Beniamin
Steinberger, Joseph
Brodsky, Sagie
Jana, Tamar
Barkai, Naama
author_facet Jonas, Felix
Carmi, Miri
Krupkin, Beniamin
Steinberger, Joseph
Brodsky, Sagie
Jana, Tamar
Barkai, Naama
author_sort Jonas, Felix
collection PubMed
description Intrinsically disordered regions (IDRs) direct transcription factors (TFs) towards selected genomic occurrences of their binding motif, as exemplified by budding yeast's Msn2. However, the sequence basis of IDR-directed TF binding selectivity remains unknown. To reveal this sequence grammar, we analyze the genomic localizations of >100 designed IDR mutants, each carrying up to 122 mutations within this 567-AA region. Our data points at multivalent interactions, carried by hydrophobic—mostly aliphatic—residues dispersed within a disordered environment and independent of linear sequence motifs, as the key determinants of Msn2 genomic localization. The implications of our results for the mechanistic basis of IDR-based TF binding preferences are discussed.
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spelling pubmed-102502222023-06-10 The molecular grammar of protein disorder guiding genome-binding locations Jonas, Felix Carmi, Miri Krupkin, Beniamin Steinberger, Joseph Brodsky, Sagie Jana, Tamar Barkai, Naama Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Intrinsically disordered regions (IDRs) direct transcription factors (TFs) towards selected genomic occurrences of their binding motif, as exemplified by budding yeast's Msn2. However, the sequence basis of IDR-directed TF binding selectivity remains unknown. To reveal this sequence grammar, we analyze the genomic localizations of >100 designed IDR mutants, each carrying up to 122 mutations within this 567-AA region. Our data points at multivalent interactions, carried by hydrophobic—mostly aliphatic—residues dispersed within a disordered environment and independent of linear sequence motifs, as the key determinants of Msn2 genomic localization. The implications of our results for the mechanistic basis of IDR-based TF binding preferences are discussed. Oxford University Press 2023-03-20 /pmc/articles/PMC10250222/ /pubmed/36938874 http://dx.doi.org/10.1093/nar/gkad184 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Jonas, Felix
Carmi, Miri
Krupkin, Beniamin
Steinberger, Joseph
Brodsky, Sagie
Jana, Tamar
Barkai, Naama
The molecular grammar of protein disorder guiding genome-binding locations
title The molecular grammar of protein disorder guiding genome-binding locations
title_full The molecular grammar of protein disorder guiding genome-binding locations
title_fullStr The molecular grammar of protein disorder guiding genome-binding locations
title_full_unstemmed The molecular grammar of protein disorder guiding genome-binding locations
title_short The molecular grammar of protein disorder guiding genome-binding locations
title_sort molecular grammar of protein disorder guiding genome-binding locations
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10250222/
https://www.ncbi.nlm.nih.gov/pubmed/36938874
http://dx.doi.org/10.1093/nar/gkad184
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