Guest editorial: Transcriptional control in myeloid cell development and related diseases.

Abstract

four review articles focusing on the biology of these important transcriptional regulators. Rapid advances in recent years in high-throughput experimental techniques, including microarrays, next-generation sequencing (such as chromatin immunoprecipitation sequencing and RNA sequencing), and high-sensitivity mass spectrometry, as well as developments in bioinformatics, have ushered in a new era in the study of transcriptional control. Comprehensive gene expression profiles and even the precise locations of transcription regulator binding and chromatin modifications throughout the genome can now be obtained. Systematic identification of the components of large protein complexes is also now achievable. Using such techniques, research into transcriptional control in myeloid cell development and related diseases has produced major advances in recent years. In the first of the four reviews, Bonifer and colleagues provide an update on the developmental stage-specific function of RUNX1 and its important target, PU.1, during myelopoiesis from both cellular and molecular aspects. They also describe the close relationship between these two critical factors, which show reciprocal regulation of gene expression and synergistic function. Moreover, these authors summarize the known mutations and translocations involving RUNX1 or PU.1, as well as the ‘addiction’ to naive RUNX1 and PU.1 in the development of acute myeloid leukemia (AML) [1]. Friedman describes the molecular basis of how C/ EBPα activates transcription as a homodimer and through its interactions with other bZIP transcription factors, such as AP-1, during myelopoiesis. The role of C/EBPα in the development of myeloid cells, particularly granulocytes and monocytes, and in the regulation of the cell cycle, survival, and quiescence, is highlighted. Moreover, Friedman summarizes the known mutations in CEBPA, the The diverse cell types of the body exhibit distinct morphologies and functions, despite the fact that (with the exception of antigen receptor genes in lymphocytes) the genome sequence is essentially identical among all cell types in an individual. The molecular basis for this diversity is that among the approximately 22,000 genes encoded by the human genome, only a specific set is expressed in a given cell type. The differentiation of stem or progenitor cells to mature cells is a sequential process of activation, inactivation, or maintenance of the selected genes—i.e., transcriptional control—that ultimately determines cell fate. Numerous studies have shown that transcription factors and epigenetic regulators play essential roles in cell differentiation. Dysregulation of these processes can result in various diseases, including cancers, such as leukemias in the case of hematopoiesis. Myeloid cells, e.g., granulocytes, monocytes/macrophages, dendritic cells, and mast cells, are generated from hematopoietic stem cells in the bone marrow via multipotent progenitors, common myeloid progenitors, granulocyte–monocyte progenitors, and more committed progenitors. Multiple factors have been identified as essential for the regulation of myelopoiesis. These include the transcription factors runt-related transcription factor 1 (RUNX1), PU.1, CCAAT/enhancer binding proteins (C/ EBPs), and interferon regulatory factor-8 (IRF8), and the chromatin regulator mixed-lineage leukemia (MLL). In this issue of International Journal of Hematology, we present Transcriptional control in myeloid cell development and related diseases