RUNX proteins in transcription factor networks that regulate T-cell lineage choice

Runx proteins (also known as Runt-domain transcription factors) have been studied for a long time as key regulators of cellular differentiation. RUNX2 has been described as essential for osteogenesis, whereas RUNX1 and RUNX3 are known to control blood cell development during different stages of cell lineage specification. However, recent studies show evidence of complex relationships between RUNX proteins, chromatin-modifying machinery, the cytoskeleton and different transcription factors in various non-embryonic contexts, including mature T cell homeostasis, inflammation and cancer. In this review, we discuss the diversity of Runx functions in mature T helper cells, such as production of cytokines and chemokines by different CD4 T cell populations; apoptosis; and immunologic memory acquisition. We then briefly cover recent findings about the contribution of RUNX1, RUNX2 and RUNX3 to various immunologic diseases. Finally, we discuss areas that require further study to better understand the role that Runx proteins play in inflammation and immunity.

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Faculty Opinions recommendation of Regulatory T cell lineage specification by the forkhead transcription factor foxp3.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1024917.298768 ◽

2005 ◽

Author(s):

Christopher Karp

Keyword(s):

Transcription Factor ◽

T Cell ◽

Regulatory T Cell ◽

Cell Lineage ◽

Forkhead Transcription Factor ◽

Lineage Specification

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Faculty Opinions recommendation of Regulatory T cell lineage specification by the forkhead transcription factor foxp3.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1024917.297730 ◽

2005 ◽

Author(s):

Santa Jeremy Ono

Keyword(s):

Transcription Factor ◽

T Cell ◽

Regulatory T Cell ◽

Cell Lineage ◽

Forkhead Transcription Factor ◽

Lineage Specification

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Faculty Opinions recommendation of An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.4168956.3956054 ◽

2010 ◽

Author(s):

Avinash Bhandoola ◽

Brittany Teague-Weber

Keyword(s):

Transcription Factor ◽

T Cell ◽

Cell Lineage ◽

Lineage Commitment

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Induction of the POU domain transcription factor Oct-2 during T-cell activation by cognate antigen

Molecular and Cellular Biology ◽

10.1128/mcb.12.7.3149-3154.1992 ◽

1992 ◽

Vol 12 (7) ◽

pp. 3149-3154

Author(s):

S M Kang ◽

W Tsang ◽

S Doll ◽

P Scherle ◽

H S Ko ◽

...

Keyword(s):

T Cells ◽

Transcription Factor ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Interleukin 2 ◽

Cell Lineage ◽

Antigen Stimulation ◽

Mrna Induction ◽

T Cell Clone

Oct-2 is a transcription factor that binds specifically to octamer DNA motifs in the promoters of immunoglobulin and interleukin-2 genes. All tumor cell lines from the B-cell lineage and a few from the T-cell lineage express Oct-2. To address the role of Oct-2 in the T-cell lineage, we studied the expression of Oct-2 mRNA and protein in nontransformed human and mouse T cells. Oct-2 was found in CD4+ and CD8+ T cells prepared from human peripheral blood and in mouse lymph node T cells. In a T-cell clone specific for pigeon cytochrome c in the context of I-Ek, Oct-2 was induced by antigen stimulation, with the increase in Oct-2 protein seen first at 3 h after activation and continuing for at least 24 h. Oct-2 mRNA induction during antigen-driven T-cell activation was blocked by cyclosporin A, as well as by protein synthesis inhibitors. These results suggest that Oct-2 participates in transcriptional regulation during T-cell activation. The relatively delayed kinetics of Oct-2 induction suggests that Oct-2 mediates the changes in gene expression which occur many hours or days following antigen stimulation of T lymphocytes.

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The transcription factor E2A activates multiple enhancers that drive Rag expression in developing T and B cells

Science Immunology ◽

10.1126/sciimmunol.abb1455 ◽

2020 ◽

Vol 5 (51) ◽

pp. eabb1455 ◽

Cited By ~ 1

Author(s):

Kazuko Miyazaki ◽

Hitomi Watanabe ◽

Genki Yoshikawa ◽

Kenian Chen ◽

Reiko Hidaka ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

T Cell ◽

B Cells ◽

Cell Lineage ◽

Cell Receptor ◽

Regulatory Elements ◽

Mouse Strains ◽

Specific Gene ◽

T And B Cells

Cell type–specific gene expression is driven by the interplay between lineage-specific transcription factors and cis-regulatory elements to which they bind. Adaptive immunity relies on RAG-mediated assembly of T cell receptor (TCR) and immunoglobulin (Ig) genes. Although Rag1 and Rag2 expression is largely restricted to adaptive lymphoid lineage cells, it remains unclear how Rag gene expression is regulated in a cell lineage–specific manner. Here, we identified three distinct cis-regulatory elements, a T cell lineage–specific enhancer (R-TEn) and the two B cell–specific elements, R1B and R2B. By generating mice lacking either R-TEn or R1B and R2B, we demonstrate that these distinct sets of regulatory elements drive the expression of Rag genes in developing T and B cells. What these elements have in common is their ability to bind the transcription factor E2A. By generating a mouse strain that carries a mutation within the E2A binding site of R-TEn, we demonstrate that recruitment of E2A to this site is essential for orchestrating changes in chromatin conformation that drive expression of Rag genes in T cells. By mapping cis-regulatory elements and generating multiple mouse strains lacking distinct enhancer elements, we demonstrate expression of Rag genes in developing T and B cells to be driven by distinct sets of E2A-dependent cis-regulatory modules.

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