Interchromosomal interaction of homologous Stat92E alleles regulates transcriptional switch during stem-cell differentiation.

Interchromosomal interaction of homologous Stat92E alleles regulates transcriptional switch during stem-cell differentiation.
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DOI:
10.1038/s41467-022-31737-y
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发表时间:
2022-07-09
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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体细胞中同源染色体的配对为同源基因区域之间的染色体间相互作用提供了机会。在果蝇雄性生殖系中,Stat 92 E基因在生殖系干细胞(GSC)中高度表达,并在分化过程中逐渐下调。在这里,我们发现Stat 92 E的配对在GSC中总是紧密的,并且在分化的子细胞,成角细胞(GB)中立即松开。通过将一个基因座重新定位到另一个染色体或通过敲低全局配对/反配对因子来干扰Stat 92 E配对都导致Stat 92 E下调失败,这表明配对是转录下降所需的。此外,Stat 92 E增强子,而不是它的转录,需要在配对状态的变化,表明配对不是转录变化的结果。最后,我们发现Stat 92 E配对的变化依赖于GSCs不对称分裂过程中的不对称组蛋白遗传。综上所述,我们认为Stat 92 E配对状态的改变是一种内在的程序化机制,可以在干细胞分化过程中实现快速的细胞命运转换。细胞器、蛋白质和RNA的不对称遗传发生在干细胞分裂期间。在这里,作者显示了同源Stat 92 E基因座(一种干细胞特异性基因)的配对强度在不对称分裂后立即发生变化,这是由于新组蛋白向其中一个子细胞的不对称遗传,并且对于在该细胞分化时关闭基因表达非常重要。
Pairing of homologous chromosomes in somatic cells provides the opportunity of interchromosomal interaction between homologous gene regions. In the Drosophila male germline, the Stat92E gene is highly expressed in a germline stem cell (GSC) and gradually downregulated during the differentiation. Here we show that the pairing of Stat92E is always tight in GSCs and immediately loosened in differentiating daughter cells, gonialblasts (GBs). Disturbance of Stat92E pairing by relocation of one locus to another chromosome or by knockdown of global pairing/anti-pairing factors both result in a failure of Stat92E downregulation, suggesting that the pairing is required for the decline in transcription. Furthermore, the Stat92E enhancer, but not its transcription, is required for the change in pairing state, indicating that pairing is not a consequence of transcriptional changes. Finally, we show that the change in Stat92E pairing is dependent on asymmetric histone inheritance during the asymmetric division of GSCs. Taken together, we propose that the changes in Stat92E pairing status is an intrinsically programmed mechanism for enabling prompt cell fate switch during the differentiation of stem cells. Asymmetric inheritance of organelles, proteins and RNAs occurs during stem cell division. Here the authors show the strength of pairing of homologous Stat92E loci, a stem cell-specific gene, changes immediately after the asymmetric division due to asymmetric inheritance of new histones to one of the daughter cells and is important for turning off gene expression in this cell as it differentiates.
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