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Review
. 2023 Jul;44(7):530-541.
doi: 10.1016/j.it.2023.05.001. Epub 2023 May 29.

A variegated model of transcription factor function in the immune system

Kaitavjeet Chowdhary  1 , Christophe Benoist  2
Affiliations
Review

A variegated model of transcription factor function in the immune system

Kaitavjeet Chowdhary et al. Trends Immunol. 2023 Jul.

Abstract

Specific combinations of transcription factors (TFs) control the gene expression programs that underlie specialized immune responses. Previous models of TF function in immunocytes had restricted each TF to a single functional categorization [e.g., lineage-defining (LDTFs) vs. signal-dependent TFs (SDTFs)] within one cell type. Synthesizing recent results, we instead propose a variegated model of immunological TF function, whereby many TFs have flexible and different roles across distinct cell states, contributing to cell phenotypic diversity. We discuss evidence in support of this variegated model, describe contextual inputs that enable TF diversification, and look to the future to imagine warranted experimental and computational tools to build quantitative and predictive models of immunocyte gene regulatory networks.

Keywords: enhancer; gene regulation; gene regulatory network; genetic variation; master regulator; transcription factor.

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Conflict of interest statement

Declaration of interests None declared by authors.

Figures

Figure 1:
Figure 1:
Beyond simple binding and transactivation: the diversity of TF regulatory mechanisms. Several of these mechanisms are compiled and adapted from [23,93]. GRN, gene regulatory networks.
Figure 2:
Figure 2:. Variegated Model of TF function.
Under this model, instead of each TF having uniform, monomorphic activity across all phenotypic cell states, TFs can have flexible, variegated functions across different settings.
Figure 3:
Figure 3:. Theoretical mechanisms of TF-TF interactions and crosstalk: how one TF can modify the activity of another.
The schematics depict how a secondary TF (“TF2”) or cofactor can modify the activity of a first TF (“TF1”), directly or indirectly.
See this image and copyright information in PMC

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