Transcription factor YY1 is essential for iNKT cell development

Transcription factor YY1 is essential for iNKT cell development
Title:
Transcription factor YY1 is essential for iNKT cell development
Other Titles:
Cellular & Molecular Immunology
Publication Date:
02 March 2018
Citation:
Ou, X., Huo, J., Huang, Y. et al. Transcription factor YY1 is essential for iNKT cell development. Cell Mol Immunol 16, 547–556 (2019). https://doi.org/10.1038/s41423-018-0002-6
Abstract:
Invariant natural killer T (iNKT) cells develop from CD4+CD8+ double-positive (DP) thymocytes and express an invariant Vα14-Jα18 T-cell receptor (TCR) α-chain. Generation of these cells requires the prolonged survival of DP thymocytes to allow for Vα14-Jα18 gene rearrangements and strong TCR signaling to induce the expression of the iNKT lineage-specific transcription factor PLZF. Here, we report that the transcription factor Yin Yang 1 (YY1) is essential for iNKT cell formation. Thymocytes lacking YY1 displayed a block in iNKT cell development at the earliest progenitor stage. YY1-deficient thymocytes underwent normal Vα14-Jα18 gene rearrangements, but exhibited impaired cell survival. Deletion of the apoptotic protein BIM failed to rescue the defect in iNKT cell generation. Chromatin immunoprecipitation and deep-sequencing experiments demonstrated that YY1 directly binds and activates the promoter of the Plzf gene. Thus, YY1 plays essential roles in iNKT cell development by coordinately regulating cell survival and PLZF expression.
License type:
PublisherCopyrights
Funding Info:
This research is supported by Bioprocessing Technology Institute, A*STAR
Description:
ISSN:
1672-7681
2042-0226
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