Divergent roles of HDAC1 and HDAC2 in the regulation of epidermal development and tumorigenesis
Autor: | Dominique Meunier, Christina Humer, Mirjam A. Moser, Simon Weissmann, Gerald Brosch, Christian Seiser, Carina Fischer, Mircea Winter, Katharina Mattes, Patrick Matthias, Beate M. Lichtenberger, Reinhard Brunmeir, Georg Machat, Maria Sibilia, Tina Meischel, Christina Murko |
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Rok vydání: | 2013 |
Předmět: |
animal structures
Transgene medicine.disease_cause General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine medicine Molecular Biology 030304 developmental biology Regulation of gene expression 0303 health sciences integumentary system General Immunology and Microbiology biology Epidermis (botany) Histone deacetylase 2 General Neuroscience Hair follicle HDAC1 enzymes and coenzymes (carbohydrates) medicine.anatomical_structure Histone 030220 oncology & carcinogenesis embryonic structures Cancer research biology.protein biological phenomena cell phenomena and immunity Carcinogenesis |
Zdroj: | The EMBO Journal. 32:3176-3191 |
ISSN: | 0261-4189 |
Popis: | The histone deacetylases HDAC1 and HDAC2 remove acetyl moieties from lysine residues of histones and other proteins and are important regulators of gene expression. By deleting different combinations of Hdac1 and Hdac2 alleles in the epidermis, we reveal a dosage-dependent effect of HDAC1/HDAC2 activity on epidermal proliferation and differentiation. Conditional ablation of either HDAC1 or HDAC2 in the epidermis leads to no obvious phenotype due to compensation by the upregulated paralogue. Strikingly, deletion of a single Hdac2 allele in HDAC1 knockout mice results in severe epidermal defects, including alopecia, hyperkeratosis, hyperproliferation and spontaneous tumour formation. These mice display impaired Sin3A co-repressor complex function, increased levels of c-Myc protein, p53 expression and apoptosis in hair follicles (HFs) and misregulation of HF bulge stem cells. Surprisingly, ablation of HDAC1 but not HDAC2 in a skin tumour model leads to accelerated tumour development. Our data reveal a crucial function of HDAC1/HDAC2 in the control of lineage specificity and a novel role of HDAC1 as a tumour suppressor in the epidermis. |
Databáze: | OpenAIRE |
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