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At the crossroads: diverse roles of early thymocyte transcriptional regulators
Author(s) -
Anderson Michele K
Publication year - 2006
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.0105-2896.2006.00352.x
Subject(s) - biology , thymocyte , transcription factor , transcriptional regulation , t cell receptor , gene , recombinase , lineage (genetic) , myb , t cell , genetics , regulation of gene expression , microbiology and biotechnology , cell fate determination , recombination activating gene , cre recombinase , transgene , recombination , immune system , genetically modified mouse
Summary: Transcriptional regulation of T‐cell development involves successive interactions between complexes of transcriptional regulators and their binding sites within the regulatory regions of each gene. The regulatory modules that control expression of T‐lineage genes frequently include binding sites for a core set of regulators that set the T‐cell‐specific background for signal‐dependent control, including GATA‐3, Notch/CSL, c‐myb, TCF‐1, Ikaros, HEB/E2A, Ets, and Runx factors. Additional regulators in early thymocytes include PU.1, Id‐2, SCL, Spi‐B, Erg, Gfi‐1, and Gli. Many of these factors are involved in simultaneous regulation of non‐T‐lineage genes, T‐lineage genes, and genes involved in cell cycle control, apoptosis, or survival. Potential and known interactions between early thymic transcription factors such as GATA‐3, SCL, PU.1, Erg, and Spi‐B are explored. Regulatory modules involved in the expression of several critical T‐lineage genes are described, and models are presented for shifting occupancy of the DNA‐binding sites in the regulatory modules of pre‐Tα, T‐cell receptor β (TCRβ), recombinase activating genes 1 and 2 (Rag‐1/2), and CD4 during T‐cell development. Finally, evidence is presented that c‐kit, Erg, Hes‐1, and HEBAlt are expressed differently in Rag‐2 –/– thymocytes versus normal early thymocytes, which provide insight into potential regulatory interactions that occur during normal T‐cell development.