Transcription Regulation in B-Cell Development

This chapter discusses transcriptional regulatory mechanisms that promote B-lymphocyte differentiation. Transcription regulation determines which genes in the genome will be read out as messenger RNA, and thus it is essential to establish tissue-specific patterns of gene expression. Once a gene is transcribed, other form of regulation, such as RNA turnover, differential splicing, and regulated translation determine the nature of the expressed protein and whether a protein will be expressed. Finally, proteins are subjected to additional forms of regulation, such as stability, posttranslational modifications, and associations with other proteins. Lymphocytes arise continuously during the lifetime of mammals starting from a self-renewing population of bone marrow derived hematopoietic stem cells (HSCs). The transcription factor PU.1 is an ETS-domain containing DNA binding protein1 that is required for the generation of both lymphoid and myeloid lineages. Bone marrow cell cultures from PU.1 deficient mice skewed toward myeloid differentiation in vitro in the presence of high levels of ectopically expressed PU.1. In contrast, lower levels of PU.1 expression favored differentiation to the B-lymphocyte lineage.