Academic Journal
KMT5C leverages disorder to optimize cooperation with HP1 for heterochromatin retention
| العنوان: | KMT5C leverages disorder to optimize cooperation with HP1 for heterochromatin retention |
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| المؤلفون: | Knechtel, Justin W, Strickfaden, Hilmar, Missiaen, Kristal, Hadfield, Joanne D, Hendzel, Michael J, Underhill, D Alan |
| المساهمون: | Canadian Breast Cancer Foundation, Cancer Research Society, Canadian Government | Canadian Institutes of Health Research |
| المصدر: | EMBO Reports ; volume 26, issue 1, page 153-174 ; ISSN 1469-3178 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| الوصف: | A defining feature of constitutive heterochromatin compartments is the heterochromatin protein-1 (HP1) family, whose members display fast internal mobility and rapid exchange with the surrounding nucleoplasm. Here, we describe a paradoxical state for the lysine methyltransferase KMT5C characterized by rapid internal diffusion but minimal nucleoplasmic exchange. This retentive behavior is conferred by sparse sequence features that constitute two modules tethered by an intrinsically disordered linker. While both modules harbor variant HP1 interaction motifs, the first comprises adjacent sequences that increase affinity using avidity. The second motif increases HP1 effective concentration to further enhance affinity in a context-dependent manner, which is evident using distinct heterochromatin recruitment strategies and heterologous linkers with defined conformational ensembles. Despite the linker sequence being highly divergent, it is under evolutionary constraint for functional length, suggesting conformational buffering can support cooperativity between modules across distant orthologs. Overall, we show that KMT5C has evolved a robust tethering strategy that uses minimal sequence determinants to harness highly dynamic HP1 proteins for retention within heterochromatin compartments. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s44319-024-00320-5 |
| الاتاحة: | https://doi.org/10.1038/s44319-024-00320-5 https://www.embopress.org/doi/epdf/10.1038/s44319-024-00320-5 https://www.embopress.org/doi/full/10.1038/s44319-024-00320-5 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.95D3DB0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s44319-024-00320-5 |
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