Research Article

Blocking promiscuous activation at cryptic promoters directs cell type–specific gene expression

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Science  19 May 2017:
Vol. 356, Issue 6339, pp. 717-721
DOI: 10.1126/science.aal3096

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Blocking somatic genes to make sperm

To generate cells with a specific identity, only a subset of genes is used. Most studies focus on factors that turn on cell type–specific gene expression. However, mechanisms are also needed to block expression of genes that specify other cell lineages. Kim et al. identified such a mechanism in the Drosophila male germ line. A multiple–zinc finger protein and a chromatin remodeler were found to act together to block transcription from cryptic promoters. These factors prevented aberrant gene expression and enabled proper differentiation in the adult sperm stem cell lineage.

Science, this issue p. 717


To selectively express cell type–specific transcripts during development, it is critical to maintain genes required for other lineages in a silent state. Here, we show in the Drosophila male germline stem cell lineage that a spermatocyte-specific zinc finger protein, Kumgang (Kmg), working with the chromatin remodeler dMi-2 prevents transcription of genes normally expressed only in somatic lineages. By blocking transcription from normally cryptic promoters, Kmg restricts activation by Aly, a component of the testis-meiotic arrest complex, to transcripts for male germ cell differentiation. Our results suggest that as new regions of the genome become open for transcription during terminal differentiation, blocking the action of a promiscuous activator on cryptic promoters is a critical mechanism for specifying precise gene activation.

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