德洛索菲拉干细胞对素H2B泛胺蛋白酶有着共同的需求
Michael Buszczak1, Shelley Paterno, Allan C Spradling
1Howard Hughes Medical Institute Research Laboratories, Department of Embryology, Carnegie Institution, Baltimore, MD 21218, USA.
Science (New York, N.Y.)
|November 29, 2008
概括
一个新发现的基因scrawny (scny) 作为一种特定于乌比奎丁的蛋白酶,对维护各种组织的干细胞功能至关重要. 它通过调节组素修饰来抑制过早分化的基因表达.
科学领域:
- 干细胞生物学 干细胞生物学
- 染色体的调节 染色体调节
- 分子遗传学 分子遗传学
背景情况:
- 干细胞需要特定的染色质状态才能自我更新.
- 已知很少有染色蛋白调节多种干细胞类型.
- 基因组蛋白修饰在基因调节和细胞命运决定中起着至关重要的作用.
研究的目的:
- 为了确定各种干细胞群体所必需的新型染色体调节剂.
- 阐明Drosophila基因在干细胞维护中的功能.
- 调查基因素无处不在在干细胞自我更新和分化中的作用.
主要方法:
- 鉴定和特征的Drosophila瘦 (瘦) 基因.
- 在生殖系,上皮和肠道干细胞中分析SCNY功能.
- 生物化学试验,以评估素H2B的脱化活性.
- 在微型突变细胞中检查基因组修饰水平 (ubiquitinylated H2B,trimethylated H3K4).
主要成果:
- 德洛索菲拉粗瘦 (scny) 基因编码了一个全方位素特异性蛋白酶.
- 瘦身是生殖线,上皮和肠道干细胞自我更新所需的.
- 斯克拉尼二维基化基因组H2B,在基因沉默中起作用.
- 微型突变细胞呈现出化H2B和三甲基化H3K4水平的增加.
- scny在含有基因组修饰的染色质调节的保存途径中起作用.
结论:
- 通过scny抑制基因组H2B无处不在是一种抑制干细胞过早分化基因表达的常见机制.
- 这种机制涉及到基特异性蛋白酶,对于维持干细胞多能性和防止异常分化至关重要.
- 这些发现突出了scny在调节关键分化基因 (包括Notch点基因) 中,在不同类型的干细胞中发挥的保留作用.
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