دورية أكاديمية
Acetylation-Specific Interference by Anti-Histone H3K9ac Intrabody Results in Precise Modulation of Gene Expression
| العنوان: | Acetylation-Specific Interference by Anti-Histone H3K9ac Intrabody Results in Precise Modulation of Gene Expression |
|---|---|
| المؤلفون: | Lisi, Simonetta, Trovato, Matteo, Vitaloni, Ottavia, Fantini, Marco, Chirichella, Michele, Tognini, Paola, Cornuti, Sara, Costa, Mario, Groth, Marco, Cattaneo, Antonino |
| المساهمون: | Lisi, Simonetta, Trovato, Matteo, Vitaloni, Ottavia, Fantini, Marco, Chirichella, Michele, Tognini, Paola, Cornuti, Sara, Costa, Mario, Groth, Marco, Cattaneo, Antonino |
| سنة النشر: | 2022 |
| المجموعة: | ARPI - Archivio della Ricerca dell'Università di Pisa |
| مصطلحات موضوعية: | HAT inhibitors (HATi), epigenetic word, histone acetyltransferases HAT, intracellular antibodie, post-translational modifications (PTMs), Acetylation, Animal, Epigenesis, Genetic, Gene Expression, Histone Acetyltransferase, Mammal, Protein Processing, Post-Translational, Histone, Lysine |
| الوصف: | Among Histone post-translational modifications (PTMs), lysine acetylation plays a pivotal role in the epigenetic regulation of gene expression, mediated by chromatin modifying enzymes. Due to their activity in physiology and pathology, several chemical compounds have been developed to inhibit the function of these proteins. However, the pleiotropy of these classes of proteins represents a weakness of epigenetic drugs. Ideally, a new generation of epigenetic drugs should target with molecular precision individual acetylated lysines on the target protein. We exploit a PTM-directed interference, based on an intrabody (scFv-58F) that selectively binds acetylated lysine 9 of histone H3 (H3K9ac), to test the hypothesis that targeting H3K9ac yields more specific effects than inhibiting the corresponding HAT enzyme that installs that PTM. In yeast scFv-58F modulates, gene expression in a more specific way, compared to two well-established HAT inhibitors. This PTM-specific interference modulated expression of genes involved in ribosome biogenesis and function. In mammalian cells, the scFv-58F induces exclusive changes in the H3K9ac-dependent expression of specific genes. These results suggest the H3K9ac-specific intrabody as the founder of a new class of molecules to directly target histone PTMs, inverting the paradigm from inhibiting the writer enzyme to acting on the PTM. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/36012156; info:eu-repo/semantics/altIdentifier/wos/WOS:000845868700001; volume:23; issue:16; numberofpages:18; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; https://hdl.handle.net/11568/1151399Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85137127376; https://www.mdpi.com/1422-0067/23/16/8892Test |
| DOI: | 10.3390/ijms23168892 |
| الإتاحة: | https://doi.org/10.3390/ijms23168892Test https://hdl.handle.net/11568/1151399Test https://www.mdpi.com/1422-0067/23/16/8892Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.2E0EB08C |
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