Transcriptional regulation of hemopoiesis

The regulation of blood cell formation, or hemopoiesis, is central to the r eplenishment of mature effector cells of innate and acquired immune respons es. These cells fulfil specific roles in the host defense against invading pathogens, and in the maintenance of homeostasis. The development of hemopo ietic cells is under stringent control from extracellular and intracellular stimuli that result in the activation of specific downstream signaling cas cades. Ultimately, all signal transduction pathways converge at the level o f gene expression where positive and negative modulators of transcription i nteract to delineate the pattern of gene expression and the overall cellula r hemopoietic response. Transcription factors, therefore, represent a nodal point of hemopoietic control through the integration of the various signal ing pathways and subsequent modulation of the transcriptional machinery. Tr anscription factors can act both positively and negatively to regulate the expression of a wide range of hemopoiesis-relevant genes including growth f actors and their receptors, other transcription factors, as well as various molecules important for the function of developing cells. The expression o f these genes is dependent on the complex interactions between transcriptio n factors, co-regulatory molecules, and specific binding sequences on the D NA. Recent advances in various vertebrate and invertebrate systems emphasiz e the importance of transcription factors for hemopoiesis control and the e volutionary conservation of several of such mechanisms. In this review we o utline some of the key issues frequently identified in studies of the trans criptional regulation of hemopoietic gene expression. In teleosts, we expec t that the characterization of several of these transcription factors and t heir regulatory mechanisms will complement recent advances in a number of f ish systems where identification of cytokine and other hemopoiesis-relevant factors are currently under investigation. (C) 2001 Elsevier Science Ltd. All rights reserved.