Distal regions of the human IFNG locus direct cell-type specific expression (88.12)

Abstract

Abstract Genes, such as IFNG, which are expressed in multiple cell lineages of the immune system, may employ a common set of regulatory elements to direct transcription in multiple cell types or individual regulatory elements to direct expression in individual cell lineages. By employing a BAC transgenic system, we demonstrate that IFNG employs unique regulatory elements to achieve lineage specific transcriptional control. Specifically, a one 1-kb element 30 kb upstream of IFNG activates transcription in T cells and NKT cells but not NK cells, macrophages and dendritic cells. This distal regulatory element is a Runx3 binding site in Th1 cells, and is needed for RNA polymerase II recruitment to IFNG, but not for histone acetylation of the IFNG locus. These results support a model whereby IFNG utilizes distinct regulatory elements to achieve cell-type expression.