The histone methyltransferase Setd8 acts in concert with c-Myc and is required to maintain skin.
The histone methyltransferase Setd8 acts in concert with c-Myc and is required to maintain skin.
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DOI：
10.1038/emboj.2011.421
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发表时间：
2012-02-01
期刊：
影响因子：
11.4
通讯作者：
Frye, Michaela
中科院分区：
文献类型：
--
作者：
Driskell, Iwona;Oda, Hisanobu;Blanco, Sandra;Nascimento, Elisabete;Humphreys, Peter;Frye, Michaela
Setd8/PR-Set7/KMT5a 依赖的组蛋白 H4 在赖氨酸 20 处的单甲基化对于培养细胞的有丝分裂至关重要；然而，Setd8 在复杂哺乳动物组织中的功能作用尚不清楚。我们使用皮肤作为模型系统来探索 Setd8 如何调节体内细胞分裂。小鼠表皮未分化层中 Setd8 的缺失会损害增殖和分化过程。如果没有 Setd8，长寿的表皮祖细胞就会丢失，导致皮脂腺和滤泡间表皮不可逆地丢失。我们证明 Setd8 是 c-Myc 的转录靶标，也是 Myc 诱导的表皮分化的重要介质。 c-Myc 过表达皮肤中 Setd8 的缺失会阻碍增殖和分化并导致细胞凋亡。细胞凋亡增加可以通过我们的发现来解释：p63（表皮定型的重要转录因子）丢失，而 p53 在 Setd8 去除后获得。 p63 的过表达和 p53 的缺失都可以挽救 Setd8 诱导的细胞凋亡。因此，Setd8是皮肤细胞凋亡的重要抑制剂，其活性对于表皮干细胞的存活、增殖和分化至关重要。
Setd8/PR-Set7/KMT5a-dependent mono-methylation of histone H4 at lysine 20 is essential for mitosis of cultured cells; yet, the functional roles of Setd8 in complex mammalian tissues are unknown. We use skin as a model system to explore how Setd8 may regulate cell division in vivo. Deletion of Setd8 in undifferentiated layers of the mouse epidermis impaired both proliferation and differentiation processes. Long-lived epidermal progenitor cells are lost in the absence of Setd8, leading to an irreversible loss of sebaceous glands and interfollicular epidermis. We show that Setd8 is a transcriptional target of c-Myc and an essential mediator of Myc-induced epidermal differentiation. Deletion of Setd8 in c-Myc-overexpressing skin blocks proliferation and differentiation and causes apoptosis. Increased apoptosis may be explained by our discovery that p63, an essential transcription factor for epidermal commitment is lost, while p53 is gained upon removal of Setd8. Both overexpression of p63 and deletion of p53 rescue Setd8-induced apoptosis. Thus, Setd8 is a crucial inhibitor of apoptosis in skin and its activity is essential for epidermal stem cell survival, proliferation and differentiation.
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影响因子：
4.8
作者：
Houston, Sabrina I.;McManus, Kirk J.;Rice, Judd C.
通讯作者：
Rice, Judd C.
影响因子：
16
作者：
Abbas T;Shibata E;Park J;Jha S;Karnani N;Dutta A
通讯作者：
Dutta A
影响因子：
14.9
作者：
Greasley, PJ;Bonnard, C;Amati, B
通讯作者：
Amati, B
DOI：
10.1083/jcb.200706150
发表时间：
2007-12-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jørgensen S;Elvers I;Trelle MB;Menzel T;Eskildsen M;Jensen ON;Helleday T;Helin K;Sørensen CS
通讯作者：
Sørensen CS
影响因子：
16
作者：
Centore RC;Havens CG;Manning AL;Li JM;Flynn RL;Tse A;Jin J;Dyson NJ;Walter JC;Zou L
通讯作者：
Zou L