Transcriptional regulation of hemopoiesis

The regulation of blood cell formation, or hemopoiesis, is central to the replenishment of mature effector cells of innate and acquired immune responses. These cells fulfil specific roles in the host defense against invading pathogens, and in the maintenance of homeostasis. The development of hemopoietic cells is under stringent control from extracellular and intracellular stimuli that result in the activation of specific downstream signaling cascades. Ultimately, all signal transduction pathways converge at the level of gene expression where positive and negative modulators of transcription interact to delineate the pattern of gene expression and the overall cellular hemopoietic response. Transcription factors, therefore, represent a nodal point of hemopoietic control through the integration of the various signaling pathways and subsequent modulation of the transcriptional machinery. Transcription factors can act both positively and negatively to regulate the expression of a wide range of hemopoiesis-relevant genes including growth factors and their receptors, other transcription factors, as well as various molecules important for the function of developing cells. The expression of these genes is dependent on the complex interactions between transcription factors, co-regulatory molecules, and specific binding sequences on the DNA. Recent advances in various vertebrate and invertebrate systems emphasize the importance of transcription factors for hemopoiesis control and the evolutionary conservation of several of such mechanisms. In this review we outline some of the key issues frequently identified in studies of the transcriptional regulation of hemopoietic gene expression. In teleosts, we expect that the characterization of several of these transcription factors and their regulatory mechanisms will complement recent advances in a number of fish systems where identification of cytokine and other hemopoiesis-relevant factors are currently under investigation. (C) 2001 Elsevier Science Ltd. All rights reserved.