Lécuyer Eric, Hoang Trang
Institut de Recherche en Immunovirologie et Cancérologie (IRIC), Montreal, Quebec, Canada.
Exp Hematol. 2004 Jan;32(1):11-24. doi: 10.1016/j.exphem.2003.10.010.
In the hematopoietic system, lineage commitment and differentiation is controlled by the combinatorial action of transcription factors from diverse families. SCL is a basic helix-loop-helix transcription factor that is an essential regulator at several levels in the hematopoietic hierarchy and whose inappropriate regulation frequently contributes to the development of pediatric T-cell acute lymphoblastic leukemia. This review discusses advances that have shed important light on the functions played by SCL during normal hematopoiesis and leukemogenesis and have revealed an unexpected robustness of hematopoietic stem cell function. Molecular studies have unraveled a mechanism through which gene expression is tightly controlled, as SCL functions within multifactorial complexes that exhibit an all-or-none switch-like behavior in transcription activation, arguing for a quantal process that depends on the concurrent occupation of target loci by all members of the complex. Finally, variations in composition of SCL-containing complexes may ensure flexibility and specificity in the regulation of lineage-specific programs of gene expression, thus providing the molecular basis through which SCL exerts its essential functions at several branch points of the hematopoietic hierarchy.
在造血系统中，谱系定向和分化受来自不同家族的转录因子的组合作用控制。SCL是一种碱性螺旋-环-螺旋转录因子，是造血层级中多个水平的关键调节因子，其调控异常常导致小儿T细胞急性淋巴细胞白血病的发生。本综述讨论了一些进展，这些进展为SCL在正常造血和白血病发生过程中所起的作用提供了重要线索，并揭示了造血干细胞功能出人意料的稳健性。分子研究揭示了一种严格控制基因表达的机制，因为SCL在多因子复合物中发挥作用，这些复合物在转录激活中表现出全或无的开关样行为，这表明这是一个定量过程，取决于复合物所有成员对靶位点的同时占据。最后，含SCL复合物组成的变化可能确保基因表达谱系特异性程序调控的灵活性和特异性，从而为SCL在造血层级的多个分支点发挥其关键功能提供分子基础。
