Interaction of the epigenetic integrator UHRF1 with the MYST domain of TIP60 inside the cell
| Autor: | Yves Mély, Waseem Ashraf, Abdulkhaleg Ibrahim, Christian Bronner, Ali Hamiche, Marc Mousli, Mahmoud Alhosin, Tanveer Ahmad, Liliyana Zaayter, Ludovic Richert |
|---|---|
| Přispěvatelé: | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
0301 basic medicine Cancer Research Cell division Fluorescence lifetime imaging microscopy (FLIM) Ubiquitin-Protein Ligases Cell cycle lcsh:RC254-282 Lysine Acetyltransferase 5 Chromatin remodeling Epigenesis Genetic Protein–protein interaction 03 medical and health sciences Protein-protein interaction Protein Domains [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Humans Epigenetics UHRF1 ComputingMilieux_MISCELLANEOUS Cancer Zinc finger Chemistry Research Methylation DNA Methylation lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Fluorescence resonance energy transfer (FRET) Cell biology 030104 developmental biology Oncology DNA methylation CCAAT-Enhancer-Binding Proteins TIP60 HeLa Cells Protein Binding |
| Zdroj: | Journal of Experimental & Clinical Cancer Research, Vol 36, Iss 1, Pp 1-14 (2017) Journal of experimental & clinical cancer research Journal of experimental & clinical cancer research, BioMed Central, 2017, 36 (1), ⟨10.1186/s13046-017-0659-1⟩ Journal of Experimental & Clinical Cancer Research : CR |
| ISSN: | 1756-9966 |
| DOI: | 10.1186/s13046-017-0659-1 |
| Popis: | Background The nuclear epigenetic integrator UHRF1 is known to play a key role with DNMT1 in maintaining the DNA methylation patterns during cell division. Among UHRF1 partners, TIP60 takes part in epigenetic regulations through its acetyltransferase activity. Both proteins are involved in multiple cellular functions such as chromatin remodeling, DNA damage repair and regulation of stability and activity of other proteins. The aim of this work was to investigate the interaction between UHRF1 and TIP60 in order to elucidate the dialogue between these two proteins. Methods Biochemical (immunoprecipitation and pull-down assays) and microscopic (confocal and fluorescence lifetime imaging microscopy; FLIM) techniques were used to analyze the interaction between TIP60 and UHRF1 in vitro and in vivo. Global methylation levels were assessed by using a specific kit. The results were statistically analyzed using Graphpad prism and Origin. Results Our study shows that UHRF1, TIP60 and DNMT1 were found in the same epigenetic macro-molecular complex. In vitro pull-down assay showed that deletion of either the zinc finger in MYST domain or deletion of whole MYST domain from TIP60 significantly reduced its interaction with UHRF1. Confocal and FLIM microscopy showed that UHRF1 co-localized with TIP60 in the nucleus and confirmed that both proteins interacted together through the MYST domain of TIP60. Moreover, overexpression of TIP60 reduced the DNA methylation levels in HeLa cells along with downregulation of UHRF1 and DNMT1. Conclusion Our data demonstrate for the first time that TIP60 through its MYST domain directly interacts with UHRF1 which might be of high interest for the development of novel oncogenic inhibitors targeting this interaction. |
| Databáze: | OpenAIRE |
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