Atchison and colleagues describes the role of an important but ubiquitously expressed transcription factor YY1 in this highly tissue-specific function (14). enhancerpromoter 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 usually modulated by the signals they receive. For instance, expression of the B cell antigen receptor (BCR) on the surface of B cells is usually 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 Jujuboside B poorly comprehended. Comparable 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 Jujuboside B 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 Jujuboside B 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 rigid negotiation between the recombination machinery and the transcriptional machinery at every developmental step. Importantly, Jujuboside B 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. == Regulation of V(D)J Recombination Role of Transcription and Chromatin == Germline configurations of antigen receptor loci in B and T lymphocytes have hundreds of variable (V) region gene-segments, which have the potential to combine with a select few diversity (D) and joining (J) gene-segments to create recombined genes encoding numerous receptors that can recognize a vast repertoire of antigens (6,7). Given the importance and timing of these events, it is no wonder that the process of V(D)J recombination is usually exquisitely regulated at multiples levels. Two exciting articles, one by Chaumeli and Skok (8) and the other by Choi and Feeney (9), review our current understanding of how transcription factors, chromatin architecture, and the three-dimensional architecture of the nucleus and the topology of genomic DNA regulate this process. An interesting article by Basu and colleagues GLP-1 (7-37) Acetate explains how ubiquitination events regulate the RAG and activation-induced cytidine deaminase (AID) enzymes that are important for recombination (10). Moreover, this article also discusses how these post-translational events also regulate DNA damage at undesirable loci and Jujuboside B during cell cycle phases (10). == Transcription Factors in Hematopoietic Development == Recombination and transcription are coupled during hematopoietic development (1113). The next set of articles deal with factors involved in this coordination. Atchison and colleagues describes the role of an important but ubiquitously expressed transcription factor YY1 in this highly tissue-specific function (14). Clark and colleagues review the function of interleukin-7 receptor (IL7R) and transcription factor STAT5 in balancing proliferation and recombination of the immunoglobulin light chain (Ig) gene (15)..