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Caenorhabditis elegans SET1/COMPASS Maintains Germline Identity by Preventing Transcriptional Deregulation Across Generations
Frontiers in Cell and Developmental Biology ( IF 4.6 ) Pub Date : 2020-08-18 , DOI: 10.3389/fcell.2020.561791
Valérie J Robert 1 , Andrew K Knutson 2 , Andreas Rechtsteiner 2 , Steven Garvis 1 , Gaël Yvert 1 , Susan Strome 2 , Francesca Palladino 1
Affiliation  

Chromatin regulators contribute to the maintenance of the germline transcriptional program. In the absence of SET-2, the Caenorhabditis elegans homolog of the SET1/COMPASS H3 Lys4 (H3K4) methyltransferase, animals show transgenerational loss of germline identity, leading to sterility. To identify transcriptional signatures associated with progressive loss of fertility, we performed expression profiling of set-2 mutant germlines across generations. We identify a subset of genes whose misexpression is first observed in early generations, a step we refer to as priming; their misexpression then further progresses in late generations, as animals reach sterility. Analysis of misregulated genes shows that down-regulation of germline genes, expression of somatic transcriptional programs, and desilencing of the X-chromosome are concurrent events leading to loss of germline identity in both early and late generations. Upregulation of transcription factor LIN-15B, the C/EBP homolog CEBP-1, and TGF-β pathway components strongly contribute to loss of fertility, and RNAi inactivation of cebp-1 and TGF-β/Smad signaling delays the onset of sterility, showing they individually contribute to maintenance of germ cell identity. Our approach therefore identifies genes and pathways whose misexpression actively contributes to the loss of germ cell fate. More generally, our data shows how loss of a chromatin regulator in one generation leads to transcriptional changes that are amplified over subsequent generations, ultimately leading to loss of appropriate cell fate.



中文翻译:


秀丽隐杆线虫 SET1/COMPASS 通过防止跨代转录失调来维持种系同一性



染色质调节因子有助于维持种系转录程序。在没有 SET-2 的情况下,秀丽隐杆线虫SET1/COMPASS H3 Lys4 (H3K4) 甲基转移酶的同源物,动物表现出种系特性的跨代丧失,导致不育。为了识别与生育力逐渐丧失相关的转录特征,我们进行了表达谱分析套装2跨代突变种系。我们确定了一个基因子集,其错误表达首先在早期世代中观察到,我们将这一步骤称为启动;随着动物达到不育状态,他们的错误表达在后代中进一步发展。对失调基因的分析表明,种系基因的下调、体细胞转录程序的表达和 X 染色体的去沉默是同时发生的事件,导致早期和晚期世代中种系身份的丧失。转录因子 LIN-15B、C/EBP 同源物 CEBP-1 和 TGF-β 途径成分的上调会强烈导致生育力丧失和 RNAi 失活。 cebp-1 TGF-β/Smad 信号传导延迟了不育的发生,表明它们各自有助于维持生殖细胞身份。因此,我们的方法确定了其错误表达会导致生殖细胞命运丧失的基因和途径。更一般地说,我们的数据显示了一代中染色质调节因子的缺失如何导致转录变化,并在后代中放大,最终导致适当的细胞命运的丧失。

更新日期:2020-09-22
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