Runx and ThPOK: a balancing act to regulate thymocyte lineage commitment.
CD4-positive helper T cells and CD8-positive cytotoxic T cells comprise the majority of T lymphocytes present in secondary lymphoid organs and are essential for acquired immunity. These two populations are derived from common precursors in the thymus and selected through interaction between their clonal T-cell receptors and major histocompatibility complex molecules. Although intensely studied as a model system for binary cell fate decisions, the mechanisms underlying the helper versus cytotoxic lineage choice in the thymus has been elusive. In the past few years, it has been demonstrated that the Runx family of transcription factors, particularly Runx3, is essential for the generation of cytotoxic lineage T cells, whereas the ThPOK zinc finger transcription factor that plays a crucial role in the differentiation of the helper lineage. Recent works have implied that a cross-regulation between Runx and ThPOK contributes to appropriate thymocyte lineage commitment. In this article, recent findings on the transcription factor networks governing thymocyte lineage decisions are discussed, focusing on the two factors, and provide insights into mechanisms of lineage-specific gene regulation in the process of T-cell commitments.
Egawa
Takeshi
T
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine at Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA. Takeshi.Egawa@med.nyu.edu
D019070:Cell Lineage; D050657:Core Binding Factor alpha Subunits / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D014157:Transcription Factors / Q000502:physiology*
D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C484225:ZBTB7B protein, human