New Inhibitors of the Human p300/CBP Acetyltransferase Are Selectively Active against the Arabidopsis HAC Proteins
Histone acetyltransferases (HATs) are involved in the epigenetic positive control of gene expression in eukaryotes. CREB-binding proteins (CBP)/p300, a subfamily of highly conserved HATs, have been shown to function as acetylases on both histones and non-histone proteins. In the model plant <i>...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10446 |
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| author | Chiara Longo Andrea Lepri Andrea Paciolla Antonella Messore Daniela De Vita Maria Carmela Bonaccorsi di Patti Matteo Amadei Valentina Noemi Madia Davide Ialongo Roberto Di Santo Roberta Costi Paola Vittorioso |
| author_facet | Chiara Longo Andrea Lepri Andrea Paciolla Antonella Messore Daniela De Vita Maria Carmela Bonaccorsi di Patti Matteo Amadei Valentina Noemi Madia Davide Ialongo Roberto Di Santo Roberta Costi Paola Vittorioso |
| author_sort | Chiara Longo |
| collection | DOAJ |
| description | Histone acetyltransferases (HATs) are involved in the epigenetic positive control of gene expression in eukaryotes. CREB-binding proteins (CBP)/p300, a subfamily of highly conserved HATs, have been shown to function as acetylases on both histones and non-histone proteins. In the model plant <i>Arabidopsis thaliana</i> among the five CBP/p300 HATs, HAC1, HAC5 and HAC12 have been shown to be involved in the ethylene signaling pathway. In addition, HAC1 and HAC5 interact and cooperate with the Mediator complex, as in humans. Therefore, it is potentially difficult to discriminate the effect on plant development of the enzymatic activity with respect to their Mediator-related function. Taking advantage of the homology of the human HAC catalytic domain with that of the Arabidopsis, we set-up a phenotypic assay based on the hypocotyl length of Arabidopsis dark-grown seedlings to evaluate the effects of a compound previously described as human p300/CBP inhibitor, and to screen previously described cinnamoyl derivatives as well as newly synthesized analogues. We selected the most effective compounds, and we demonstrated their efficacy at phenotypic and molecular level. The in vitro inhibition of the enzymatic activity proved the specificity of the inhibitor on the catalytic domain of HAC1, thus substantiating this strategy as a useful tool in plant epigenetic studies. |
| first_indexed | 2024-03-09T23:46:45Z |
| format | Article |
| id | doaj.art-6ab7a401a76f4fd5a266a202318ac20e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:46:45Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6ab7a401a76f4fd5a266a202318ac20e2023-11-23T16:41:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181044610.3390/ijms231810446New Inhibitors of the Human p300/CBP Acetyltransferase Are Selectively Active against the Arabidopsis HAC ProteinsChiara Longo0Andrea Lepri1Andrea Paciolla2Antonella Messore3Daniela De Vita4Maria Carmela Bonaccorsi di Patti5Matteo Amadei6Valentina Noemi Madia7Davide Ialongo8Roberto Di Santo9Roberta Costi10Paola Vittorioso11Department of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Chemistry and Technology of Drug, Sapienza University of Rome, Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00185 Rome, ItalyDepartment of Environmental Biology, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Chemistry and Technology of Drug, Sapienza University of Rome, Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00185 Rome, ItalyDepartment of Chemistry and Technology of Drug, Sapienza University of Rome, Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00185 Rome, ItalyDepartment of Chemistry and Technology of Drug, Sapienza University of Rome, Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00185 Rome, ItalyDepartment of Chemistry and Technology of Drug, Sapienza University of Rome, Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00185 Rome, ItalyDepartment of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyHistone acetyltransferases (HATs) are involved in the epigenetic positive control of gene expression in eukaryotes. CREB-binding proteins (CBP)/p300, a subfamily of highly conserved HATs, have been shown to function as acetylases on both histones and non-histone proteins. In the model plant <i>Arabidopsis thaliana</i> among the five CBP/p300 HATs, HAC1, HAC5 and HAC12 have been shown to be involved in the ethylene signaling pathway. In addition, HAC1 and HAC5 interact and cooperate with the Mediator complex, as in humans. Therefore, it is potentially difficult to discriminate the effect on plant development of the enzymatic activity with respect to their Mediator-related function. Taking advantage of the homology of the human HAC catalytic domain with that of the Arabidopsis, we set-up a phenotypic assay based on the hypocotyl length of Arabidopsis dark-grown seedlings to evaluate the effects of a compound previously described as human p300/CBP inhibitor, and to screen previously described cinnamoyl derivatives as well as newly synthesized analogues. We selected the most effective compounds, and we demonstrated their efficacy at phenotypic and molecular level. The in vitro inhibition of the enzymatic activity proved the specificity of the inhibitor on the catalytic domain of HAC1, thus substantiating this strategy as a useful tool in plant epigenetic studies.https://www.mdpi.com/1422-0067/23/18/10446<i>Arabidopsis thaliana</i>HAC proteinsp300/CBP inhibitors |
| spellingShingle | Chiara Longo Andrea Lepri Andrea Paciolla Antonella Messore Daniela De Vita Maria Carmela Bonaccorsi di Patti Matteo Amadei Valentina Noemi Madia Davide Ialongo Roberto Di Santo Roberta Costi Paola Vittorioso New Inhibitors of the Human p300/CBP Acetyltransferase Are Selectively Active against the Arabidopsis HAC Proteins International Journal of Molecular Sciences <i>Arabidopsis thaliana</i> HAC proteins p300/CBP inhibitors |
| title | New Inhibitors of the Human p300/CBP Acetyltransferase Are Selectively Active against the Arabidopsis HAC Proteins |
| title_full | New Inhibitors of the Human p300/CBP Acetyltransferase Are Selectively Active against the Arabidopsis HAC Proteins |
| title_fullStr | New Inhibitors of the Human p300/CBP Acetyltransferase Are Selectively Active against the Arabidopsis HAC Proteins |
| title_full_unstemmed | New Inhibitors of the Human p300/CBP Acetyltransferase Are Selectively Active against the Arabidopsis HAC Proteins |
| title_short | New Inhibitors of the Human p300/CBP Acetyltransferase Are Selectively Active against the Arabidopsis HAC Proteins |
| title_sort | new inhibitors of the human p300 cbp acetyltransferase are selectively active against the arabidopsis hac proteins |
| topic | <i>Arabidopsis thaliana</i> HAC proteins p300/CBP inhibitors |
| url | https://www.mdpi.com/1422-0067/23/18/10446 |
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