GLP-1 Notch—LAG-1 CSL control of the germline stem cell fate is mediated by transcriptional targets lst-1 and sygl-1

Autoři: Jian Chen aff001;  Ariz Mohammad aff001;  Nanette Pazdernik aff001;  Huiyan Huang aff003;  Beth Bowman aff004;  Eric Tycksen aff006;  Tim Schedl aff001
Působiště autorů: Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri, United States of America aff001;  Current address, Integrated DNA Technologies, Coralville, Iowa, United States of America aff002;  Department of Pediatrics, Washington University School of Medicine, Saint Louis, Missouri, United States of America aff003;  Department of Biology, Emory University, Atlanta, Georgia, United States of America aff004;  Current address, Vanderbilt University, Nashville, Tennessee, United States of America aff005;  Genome Technology Access Center, McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, Missouri, United States of America aff006
Vyšlo v časopise: GLP-1 Notch—LAG-1 CSL control of the germline stem cell fate is mediated by transcriptional targets lst-1 and sygl-1. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008650
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008650


Stem cell systems are essential for the development and maintenance of polarized tissues. Intercellular signaling pathways control stem cell systems, where niche cells signal stem cells to maintain the stem cell fate/self-renewal and inhibit differentiation. In the C. elegans germline, GLP-1 Notch signaling specifies the stem cell fate, employing the sequence-specific DNA binding protein LAG-1 to implement the transcriptional response. We undertook a comprehensive genome-wide approach to identify transcriptional targets of GLP-1 signaling. We expected primary response target genes to be evident at the intersection of genes identified as directly bound by LAG-1, from ChIP-seq experiments, with genes identified as requiring GLP-1 signaling for RNA accumulation, from RNA-seq analysis. Furthermore, we performed a time-course transcriptomics analysis following auxin inducible degradation of LAG-1 to distinguish between genes whose RNA level was a primary or secondary response of GLP-1 signaling. Surprisingly, only lst-1 and sygl-1, the two known target genes of GLP-1 in the germline, fulfilled these criteria, indicating that these two genes are the primary response targets of GLP-1 Notch and may be the sole germline GLP-1 signaling protein-coding transcriptional targets for mediating the stem cell fate. In addition, three secondary response genes were identified based on their timing following loss of LAG-1, their lack of a LAG-1 ChIP-seq peak and that their glp-1 dependent mRNA accumulation could be explained by a requirement for lst-1 and sygl-1 activity. Moreover, our analysis also suggests that the function of the primary response genes lst-1 and sygl-1 can account for the glp-1 dependent peak protein accumulation of FBF-2, which promotes the stem cell fate and, in part, for the spatial restriction of elevated LAG-1 accumulation to the stem cell region.

Klíčová slova:

Auxins – DNA transcription – Genomic signal processing – Germ cells – Gonads – Messenger RNA – Notch signaling – Stem cell niche


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