Immunological applications of genomics

The 2006 meeting on Gene Expression and Signaling in the Immune System at the Cold Spring Harbor Laboratory highlighted diverse aspects of signal transduction and transcriptional regulation in lymphocytes and other hematopoietic cells. We shall discuss some of the highlights of the meeting, focusing on research related to, relying on or informed in some way by genomics, including studies of long-range interactions between cis- and even trans-regulatory regions, genome-wide transcriptional profiling and RNAi screens, epigenomic analysis, and the use of RNA interference (RNAi) and microRNAs (miRNA) to study gene expression.The expression of immune-system genes is under strict control, with many of the crucial gene regulatory elements lying outside the proximal promoter regions. A number of presentations explored these distal regulatory regions and the proteins that interact with them. The specification of cell fate during the development of T lymphocytes in the thymus is associated with the differential expression of the CD4 and CD8 cell-surface co-receptor proteins, which mark two main lineages of T cells, the helper and killer (cytolytic) T cells, respectively. Expression of CD4 and CD8 is tightly controlled by cis-regulatory elements that function in a developmental stage-specific, subset-specific and lineage-specific manner. Wilfried Ellmeier (Medical University of Vienna, Austria) showed that activation of the murine Cd8 locus is associated with chromatin remodeling that is mediated in part by the Cd8 enhancers E8I and E8II, which show a high degree of cross-species conservation. Using yeast one-hybrid screens, he and his colleagues identified the BTB/POZ domain-containing zinc-finger transcription factor MAZR as a factor that binds the E8II enhancer, and showed that MAZR is a transcriptional repressor of Cd8 expression. A poster by Jamie Schoenborn and Christopher Wilson (University of Washington, Seattle, USA) described the use of two complementary approaches -