A Shared Regulatory Element Controls the Initiation of Tcf7 Expression During Early T Cell and Innate Lymphoid Cell Developments

Author:

Harly, Christelle

Kenney, Devin

Wang, Yueqiang

Ding, Yi

Zhao, Yongge

Awasthi,Roackie

Bhandoola, Avinash
Author Address

T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, United States., Universit 233; de Nantes, CNRS, Inserm, CRCINA, Nantes, France., LabEx IGO "Immunotherapy, Graft, Oncology", Nantes, France., Typhoon Biotech, BGI-Shenzhen, Shenzhen, China., Laboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, National Institute of Health, Frederick, MD, United States.,

Abstract:

The transcription factor TCF-1 (encoded by Tcf7) plays critical roles in several lineages of hematopoietic cells. In this study, we examined the molecular basis for Tcf7 regulation in T cells, innate lymphoid cells, and migratory conventional dendritic cells that we find express Tcf7. We identified a 1 kb regulatory element crucial for the initiation of Tcf7 expression in T cells and innate lymphoid cells, but dispensable for Tcf7 expression in Tcf7-expressing dendritic cells. Within this region, we identified a Notch binding site important for the initiation of Tcf7 expression in T cells but not in innate lymphoid cells. Our work establishes that the same regulatory element is used by distinct transcriptional controllers to initiate Tcf7 expression in T cells and ILCs. Copyright © 2020 Harly, Kenney, Wang, Ding, Zhao, Awasthi and Bhandoola.

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