HDAC4 degradation during senescence unleashes an epigenetic program driven by AP-1/p300 at selected enhancers and super-enhancers
| العنوان: | HDAC4 degradation during senescence unleashes an epigenetic program driven by AP-1/p300 at selected enhancers and super-enhancers |
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| المؤلفون: | Viviana Moresi, Emiliano Dalla, Liliana Ranzino, Claudio Brancolini, Eros Di Giorgio, Raffaella Picco, Martina Minisini, Harikrishnareddy Paluvai, Alessandra Renzini |
| المصدر: | Genome Biology, Vol 22, Iss 1, Pp 1-25 (2021) Genome Biology |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Senescence, BRD4, Transcription, Genetic, QH301-705.5, p300, Biology, QH426-470, SASP, Histone Deacetylases, Epigenesis, Genetic, Transcriptome, Histones, Cell Line, Tumor, Gene expression, Genetics, Humans, Epigenetics, Biology (General), Enhancer, Cells, Cultured, Cellular Senescence, H3K27, Research, Gene Expression Profiling, H3K4me1, Computational Biology, HDAC4, Acetylation, Epigenome, Fibroblasts, AP-1, Cell biology, Repressor Proteins, Transcription Factor AP-1, Enhancer Elements, Genetic, Super-enhancers, Gene Expression Regulation, OIS, Gene Knockdown Techniques, Class IIa HDACs, Proteolysis, E1A-Associated p300 Protein |
| الوصف: | Background Cellular senescence is a permanent state of replicative arrest defined by a specific pattern of gene expression. The epigenome in senescent cells is sculptured in order to sustain the new transcriptional requirements, particularly at enhancers and super-enhancers. How these distal regulatory elements are dynamically modulated is not completely defined. Results Enhancer regions are defined by the presence of H3K27 acetylation marks, which can be modulated by class IIa HDACs, as part of multi-protein complexes. Here, we explore the regulation of class IIa HDACs in different models of senescence. We find that HDAC4 is polyubiquitylated and degraded during all types of senescence and it selectively binds and monitors H3K27ac levels at specific enhancers and super-enhancers that supervise the senescent transcriptome. Frequently, these HDAC4-modulated elements are also monitored by AP-1/p300. The deletion of HDAC4 in transformed cells which have bypassed oncogene-induced senescence is coupled to the re-appearance of senescence and the execution of the AP-1/p300 epigenetic program. Conclusions Overall, our manuscript highlights a role of HDAC4 as an epigenetic reader and controller of enhancers and super-enhancers that supervise the senescence program. More generally, we unveil an epigenetic checkpoint that has important consequences in aging and cancer. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5924870c31abe1d27fef694fad3ef9e5 https://doaj.org/article/e1bf26ea795149a1901c71d8ba176257 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5924870c31abe1d27fef694fad3ef9e5 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |