At the crossroads: diverse roles of early thymocyte transcriptional regulators.
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-Talpha, T-cell receptor beta (TCRbeta), 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.
Anderson
Michele K
MK
Sunnybrook and Women's College Health Sciences Center, Division of Molecular and Cell Biology, University of Toronto, Department of Immunology, Toronto, ON, Canada. manderso@swri.ca
D000818:Animals; D018507:Gene Expression Regulation, Developmental; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D020868:Gene Silencing; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D038041:Lymphopoiesis; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D000099232:Proto-Oncogene Protein Spi-1
D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1