| First Author | Wilms C | Year | 2018 |
| Journal | Int J Mol Sci | Volume | 19 |
| Issue | 3 | PubMed ID | 29495602 |
| Mgi Jnum | J:264657 | Mgi Id | MGI:6192936 |
| Doi | 10.3390/ijms19030687 | Citation | Wilms C, et al. (2018) 2A-DUB/Mysm1 Regulates Epidermal Development in Part by Suppressing p53-Mediated Programs. Int J Mol Sci 19(3):687 |
| abstractText | Development and homeostasis of the epidermis are governed by a complex network of sequence-specific transcription factors and epigenetic modifiers cooperatively regulating the subtle balance of progenitor cell self-renewal and terminal differentiation. To investigate the role of histone H2A deubiquitinase 2A-DUB/Mysm1 in the skin, we systematically analyzed expression, developmental functions, and potential interactions of this epigenetic regulator using Mysm1-deficient mice and skin-derived epidermal cells. Morphologically, skin of newborn and young adult Mysm1-deficient mice was atrophic with reduced thickness and cellularity of epidermis, dermis, and subcutis, in context with altered barrier function. Skin atrophy correlated with reduced proliferation rates in Mysm1(-/-) epidermis and hair follicles, and increased apoptosis compared with wild-type controls, along with increases in DNA-damage marker gammaH2AX. In accordance with diminished alpha6-Integrin(high+)CD34(+) epidermal stem cells, reduced colony formation of Mysm1(-/-) epidermal progenitors was detectable in vitro. On the molecular level, we identified p53 as potential mediator of the defective Mysm1-deficient epidermal compartment, resulting in increased pro-apoptotic and anti-proliferative gene expression. In Mysm1(-/-)p53(-/-) double-deficient mice, significant recovery of skin atrophy was observed. Functional properties of Mysm1(-/-) developing epidermis were assessed by quantifying the transepidermal water loss. In summary, this investigation uncovers a role for 2A-DUB/Mysm1 in suppression of p53-mediated inhibitory programs during epidermal development. |
