ArticleDevelopment (Cambridge, England)2022
Notch-dependent DNA cis-regulatory elements and their dose-dependent control of C. elegans stem cell self-renewal.
Article in Development (Cambridge, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Genetic mutations in GLP-1/Notch pathway reveal distinct mechanisms of Notch signaling in germline stem cell regulation.Biology open · 2026Article
- Comprehensive comparative analysis of the effects of temperature on the Notch signaling response in vivo.Biology open · 2025Article
- Synthetic guide sequence to generate CRISPR-Cas9 entry strains inmicroPublication biology · 2025Article
- Aging disrupts spatiotemporal regulation of germline stem cells and niche integrity.Biology open · 2024Article
- LST-1 is a bifunctional regulator that feeds back on Notch-dependent transcription to regulateProceedings of the National Academy of Sciences of the United States of America · 2023Article
- PLAU is associated with cell migration and invasion and is regulated by transcription factor YY1 in cervical cancer.Oncology reports · 2023Article
- Analysis of the C. elegans Germline Stem Cell Pool.Methods in molecular biology (Clifton, N.J.) · 2023Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
A long-standing biological question is how DNA cis-regulatory elements shape transcriptional patterns during metazoan development. Reporter constructs, cell culture assays and computational modeling have made major contributions to answering this question, but analysis of elements in their natural context is an important complement. Here, we mutate Notch-dependent LAG-1 binding sites (LBSs) in the endogenous Caenorhabditis elegans sygl-1 gene, which encodes a key stem cell regulator, and analyze the consequences on sygl-1 expression (nascent transcripts, mRNA, protein) and stem cell maintenance. Mutation of one LBS in a three-element cluster approximately halved both expression and stem cell pool size, whereas mutation of two LBSs essentially abolished them. Heterozygous LBS mutant clusters provided intermediate values. Our results lead to two major conclusions. First, both LBS number and configuration impact cluster activity: LBSs act additively in trans and synergistically in cis. Second, the SYGL-1 gradient promotes self-renewal above its functional threshold and triggers differentiation below the threshold. Our approach of coupling CRISPR/Cas9 LBS mutations with effects on both molecular and biological readouts establishes a powerful model for in vivo analyses of DNA cis-regulatory elements.
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