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Chunk #2 — Introduction

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Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities.
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The mammalian hematopoietic system represents a well-characterized model for the analysis of the combinatorial sets of transcription factors that orchestrate the development of distinct cell types from hematopoietic stem cells. Within the hematopoietic system, macrophages and B cells play essential and complementary roles in the innate and adaptive arms of the immune system. Recent studies suggest a model in which these cell types are derived from a lymphoid-primed multipotential progenitor (LMPP) that subsequently gives rise to common lymphoid progenitor (CLP) and granulocyte-macrophage progenitor (GMP) cells (Adolfsson et al., 2005) (Fig 1A). The Ets factor PU.1 is required for the generation of both GMP and CLP, and the later stages of macrophage and B cell development are additionally dependent on a number of cell type-restricted factors. Of these, AP-1 and C/EBP family factors are required for macrophage development and function (Friedman, 2007), while E2A, EBF1, Pax5 and Oct-2 play important roles in the development and function of B cells (Medina and Singh, 2005). In addition to its roles in hematopoietic development, recent evidence suggests that PU.1-bound sites in macrophages play a