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Updated: Nov 11, 2025

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Inaccessible LCG Promoters Act as Safeguards to Restrict T Cell Development to Appropriate Notch Signaling
Suzanne Furuyama1, Qian Vicky Wu1, Barbara Varnum-Finney1
1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Abstract:
T cell development is restricted to the thymus and is dependent on high levels of Notch signaling induced within the thymic microenvironment. To understand Notch function in thymic restriction, we investigated the basis for target gene selectivity in response to quantitative differences in Notch signal strength, focusing on the chromatin architecture of genes essential for T cell differentiation. We find that high Notch signal strength is required to activate promoters of known targets essential for T cell commitment, including Il2ra, Cd3ε, and Rag1, which feature low CpG content (LCG) and DNA inaccessibility in hematopoietic stem progenitor cells. Our findings suggest that promoter DNA inaccessibility at LCG T lineage genes provides robust protection against stochastic activation in inappropriate Notch signaling contexts, limiting T cell development to the thymus.
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