Caenorhabditis elegans SET1/COMPASS Maintains Germline Identity by Preventing Transcriptional Deregulation Across Generations.
Front Cell Dev Biol, 8:561791.
Chromatin regulators contribute to the maintenance of the germline transcriptionalprogram. In the absence of SET-2, the Caenorhabditis elegans homolog of theSET1/COMPASS H3 Lys4 (H3K4) methyltransferase, animals show transgenerational lossof germline identity, leading to sterility. To identify transcriptional signaturesassociated with progressive loss of fertility, we performed expression profiling ofset-2 mutant germlines across generations. We identify a subset of genes whosemisexpression is first observed in early generations, a step we refer to as priming;their misexpression then further progresses in late generations, as animals reachsterility. Analysis of misregulated genes shows that down-regulation of germlinegenes, expression of somatic transcriptional programs, and desilencing of theX-chromosome are concurrent events leading to loss of germline identity in bothearly and late generations. Upregulation of transcription factor LIN-15B, the C/EBPhomolog CEBP-1, and TGF-β pathway components strongly contribute to loss offertility, and RNAi inactivation of cebp-1 and TGF-β/Smad signaling delays the onsetof sterility, showing they individually contribute to maintenance of germ cellidentity. Our approach therefore identifies genes and pathways whose misexpressionactively contributes to the loss of germ cell fate. More generally, our data showshow loss of a chromatin regulator in one generation leads to transcriptional changesthat are amplified over subsequent generations, ultimately leading to loss ofappropriate cell fate.
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