A novel mechanism of post-translational modulation of HMGA functions by the histone chaperone nucleophosmin
| Autor: | Antonio Brunetti, Laura Arnoldo, Stefania Iiritano, Riccardo Sgarra, Biagio Arcidiacono, Eusebio Chiefari, Ilenia Pellarin, Guidalberto Manfioletti, Silvia Pegoraro |
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| Přispěvatelé: | Arnoldo, Laura, Sgarra, Riccardo, Chiefari, Eusebio, Iiritano, Stefania, Arcidiacono, Biagio, Pegoraro, Silvia, Pellarin, Ilenia, Brunetti, Antonio, Manfioletti, Guidalberto |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Transcription
Genetic Molecular Sequence Data Regulatory Sequences Nucleic Acid Article DNA-binding Chaperones Humans Histone Chaperones Amino Acid Sequence HMGA RNA Small Interfering HMGA Proteins Promoter Regions Genetic Genetics Nucleophosmin Multidisciplinary Binding Sites biology Nuclear Proteins Promoter DNA Hep G2 Cells Chromatin Receptor Insulin Cell biology Protein Structure Tertiary Insulin-Like Growth Factor Binding Protein 1 Histone Regulatory sequence Chaperone (protein) biology.protein Multidisciplinary HMGA Chaperones Chromatin DNA-binding RNA Interference Protein Processing Post-Translational Protein Binding |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | High Mobility Group A are non-histone nuclear proteins that regulate chromatin plasticity and accessibility, playing an important role both in physiology and pathology. Their activity is controlled by transcriptional, post-transcriptional and post-translational mechanisms. In this study we provide evidence for a novel modulatory mechanism for HMGA functions. We show that HMGAs are complexed in vivo with the histone chaperone nucleophosmin (NPM1), that this interaction requires the histone-binding domain of NPM1 and that NPM1 modulates both DNA-binding affinity and specificity of HMGAs. By focusing on two human genes whose expression is directly regulated by HMGA1, the Insulin receptor (INSR) and the Insulin-like growth factor-binding protein 1 (IGFBP1) genes, we demonstrated that occupancy of their promoters by HMGA1 was NPM1-dependent, reflecting a mechanism in which the activity of these cis-regulatory elements is directly modulated by NPM1 leading to changes in gene expression. HMGAs need short stretches of AT-rich nucleosome-free regions to bind to DNA. Therefore, many putative HMGA binding sites are present within the genome. Our findings indicate that NPM1, by exerting a chaperoning activity towards HMGAs, may act as a master regulator in the control of DNA occupancy by these proteins and hence in HMGA-mediated gene expression. |
| Databáze: | OpenAIRE |
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