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

Science. 2017 May 19;356(6339):717-721. doi: 10.1126/science.aal3096.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Animals
  • Autoantigens / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Chromatin / genetics
  • Chromatin / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / genetics*
  • Female
  • Gene Expression Regulation / genetics*
  • Male
  • Organ Specificity / genetics*
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Spermatocytes / cytology
  • Spermatocytes / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Testis / cytology
  • Testis / metabolism

Substances

  • Autoantigens
  • Cell Cycle Proteins
  • Chromatin
  • Drosophila Proteins
  • Mi-2 protein, Drosophila
  • RNA, Messenger
  • aly protein, Drosophila
  • Adenosine Triphosphatases