Identification of distal regulatory regions for the human LAT gene (946.11)

Abstract

The human LAT gene encodes a transmembrane adaptor protein linking receptor engagement to the activation of downstream signaling pathways. This gene, highly conserved among mammals, is critical for the development and/or function of T cells, mast cells, Natural Killer cells, and megakaryocytes/platelets. Previously, we characterized the LAT promoter region and identified members of the Ets and Runx family of transcription factors as important regulators of LAT gene expression. In the present study, we sought to identify and characterize distal control regions that also contribute to LAT gene expression. Using a variety of criteria, including DNase hypersensitivity, sequence conservation, the presence of various histone modifications, and RNA polymerase binding, we identified three regions, either within introns or downstream of the gene, that displayed features consistent with enhancer elements. One of these regions displayed significant enhancer activity in a transient transfection assays. Further characterization of this region as well as the identification and testing of additional potential LAT enhancer regions will be presented.Grant Funding Source: NIH grant #11255497