At the crossroads: diverse roles of early thymocyte transcriptional regulators

Immunol Rev. 2006 Feb;209:191-211. doi: 10.1111/j.0105-2896.2006.00352.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation, Developmental*
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Gene Silencing
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Lymphopoiesis*
  • Mice
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • Thymus Gland / cytology
  • Thymus Gland / metabolism*
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism*
  • Transcription, Genetic

Substances

  • Interleukin-2
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Trans-Activators
  • Transcription Factors
  • proto-oncogene protein Spi-1