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

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.

The E protein-TCF1 axis controls γδ T cell development and effector fate

“…This suggests either that these E-protein-bound elements do not play a critical role in maintaining TCF1 expression in developing γδ T cells or that loss of the EPE disables the capacity of E proteins to regulate TCF1 expression through those other elements. A recent report revealed that an element nearby one of those E protein peaks plays an important role in supporting TCF1 expression in developing αβ lineage progenitors and innate lymphoid cells ( Harly et al, 2020 ), raising the possibility that different elements are used to support TCF1 expression in different cell types.…”

“…This suggests that TCF1 expression in γδ T cell progenitors is modulated by TCR-mediated induction of E protein antagonists, including Id3. This mode of regulation may be restricted to developing γδ T cell progenitors, since a distinct element appears to be utilized to support TCF1 expression in developing αβ and innate lymphoid cells ( Harly et al, 2020 ). It is also possible that this mode of regulation is important in other contexts, including the generation of memory CD8 T cells, where several E-protein-bound elements have been reported near the Tcf7 locus ( Masson et al, 2013 ; Miyazaki et al, 2017 ).…”

Role of TCF‐1 in differentiation, exhaustion, and memory of CD8 + T cells: A review

“…30 It was recently reported that a 1-kb region upstream of a TCF7 promoter initiates TCF7 expression during the early T cell development. 31 This region can be bound by many transcription factors involved in TCF7 expression in normal T cell development, such as Gata-3, Runx, and Notch. 31 In summary, TCF-1-centered network plays an indispensable role during various developmental stages of T cells.…”

In Silico Analysis of Possible Interaction between Host Genomic Transcription Factors (TFs) and Zika Virus (ZikaSPH2015) Strain with Combinatorial Gene Regulation; Virus Versus Host—The Game Reloaded

“…IRF8 is essential for development of monocytes, Plasmacytoid dendritic cells (pDCs) and Type 1 Conventional Dendritic Cells (cDC1s) [ 31 ]. SPIB is important in production of large amounts of interferon which block viral replication [ 32 ], while TCF7, predominantly expressed in T-cells, plays a critical role in natural killer cell and innate lymphoid cell development [ 33 ]. Our workflow allowd us to to take over involvement of AR (Androgen Receptor; OMIM 313700), which, when decreased in AR knockout mice, is associated with reduction of neutrophils function [ 34 ].…”