Stonewalling Drosophila stem cell differentiation by epigenetic controls
Stonewalling Drosophila stem cell differentiation by epigenetic controls
复制标题
DOI：
10.1242/dev.02810
复制
发表时间：
2007-04-15
期刊：
影响因子：
4.6
通讯作者：
McKearin, Dennis M.
中科院分区：
文献类型：
--
作者：
Maines, Jean Z.;Park, Joseph K.;McKearin, Dennis M.
在果蝇卵子发生过程中，生殖系干细胞(GSC)的特性在很大程度上是通过阻止促进分化的因子的表达来维持的。这是通过几个基因的活动完成的，这些基因要么作用于GSC，要么作用于GSC的利基。翻译抑制因子Nanos和Pumilio可能通过抑制早期分化因子的翻译在GSCs中起作用，而生态位信号通过沉默分化因子Bam的转录来阻止分化。我们发现DNA相关蛋白石墙(Stonewall，Stwl)也是GSC维持所必需的。Stwl是细胞自主必需的；stwl(-)生殖细胞的克隆因分化而丢失，异位stwl导致GSCs的扩张。Stwl突变体作为杂化的抑制因子，表明stwl正常作用于染色质依赖的基因抑制。与先前描述的几个GSC维持因子不同，Stw1可能在表观遗传上起到阻止GSC分化的作用。依赖Stwl的转录抑制不针对bam，而是Stwl抑制许多基因的表达，包括那些可能被Nanos和Pumilio翻译抑制靶向的基因。
During Drosophila oogenesis, germline stem cell (GSC) identity is maintained largely by preventing the expression of factors that promote differentiation. This is accomplished via the activity of several genes acting either in the GSC or in its niche. The translational repressors Nanos and Pumilio act in GSCs to prevent differentiation, probably by inhibiting the translation of early differentiation factors, whereas niche signals prevent differentiation by silencing transcription of the differentiation factor Bam. We have found that the DNA-associated protein Stonewall (Stwl) is also required for GSC maintenance. stwl is required cell-autonomously; clones of stwl(-) germ cells were lost by differentiation, and ectopic Stwl caused an expansion of GSCs. stwl mutants acted as Suppressors of variegation, indicating that stwl normally acts in chromatin-dependent gene repression. In contrast to several previously described GSC maintenance factors, Stwl probably functions epigenetically to prevent GSC differentiation. Stwl-dependent transcriptional repression does not target bam, but rather Stwl represses the expression of many genes, including those that may be targeted by Nanos and Pumilio translational inhibition.