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The process of generating differentiated cell types performing specific effector functions from their respective undifferentiated precursors is dictated by extracellular signals, which alter the host cell’s capacity to perform cellular functions. One major mechanism for bringing about such changes is at the level of transcription. Thus, the transcription-related induction of previously silent genes and suppression of active genes in response to extracellular signals can result in the acquisition of new functions by the cells. The general transcriptional machinery, which comprised of RNA Polymerase II and associated initiation factors, assemble into preinitiation complexes at the core promoters of eukaryotic protein coding genes in response to the signal-dependent activation of corresponding regulatory factors that bind to promoter and enhancer elements (1). The rate of formation and/or stability of these complexes, which can be modulated both by enhancer–promoter interactions and by chromatin structural modifications, dictate the transcriptional regulation of the corresponding gene. Such coordinated temporal and spatial regulation of gene expression in response to specific signals determines lineage differentiation, cellular proliferation, and development (2).  Every event in the life cycle of a lymphocyte is modulated by the signals they receive. For instance, expression of the B cell antigen receptor (BCR) on the surface of B cells is a hallmark of various stages of B cell development, with signaling through the BCR being important during both early/antigen-independent (tonic) and late/antigen-dependent phases of development (3). However, how BCR signaling connects to chromatin changes and downstream transcriptional pathways at each step of development remains poorly understood. Similar questions also remain in other cells of the immune system. In particular, how enhancers communicate with promoters in a stage-specific fashion and in the context of chromatin also remain unclear (2). Chromatin modifiers are generally present and active in most cell types (4, 5). How then could there be gene-specific differences in chromatin architecture dependent on a particular stage of development?  The B (and T) lymphocytes also perform a unique developmental program because they have an unparalleled genetic makeup – the genetic loci that encode their cell surface receptors are in an “unrearranged” or “germline” configuration during the early stages of development. Thus, while expressing stage-specific genes and transcription factors during each developmental stage, lymphocytes also need to undergo rearrangement of their cognate receptor loci in a strictly ordered fashion to generate a pool of receptor proteins that, individually, are capable of recognizing specific antigens that are encountered at a much later step (6). Hence, there must be a strict negotiation between the recombination machinery and the transcriptional machinery at every developmental step. Importantly, along the way, those B cells that express receptors capable of recognizing self-antigens must be eliminated to avoid autoimmune responses and only those cells capable of recognizing foreign-antigens are preserved for migration to peripheral organs where they eventually encounter pathogens. How are these processes coordinately regulated in a stage-specific fashion and what role does chromatin play? Are the rules of engagement different in innate versus adaptive immune responses? The following 15 articles address some of these questions and provide important insights regarding our current understanding of signal-induced chromatin and transcriptional regulation of the immune system.

Chromatin and Transcriptional Tango on the Immune Dance Floor