Distal regions of the human IFNG locus direct cell type-specific expression.

Collins PL, Chang S, Henderson M, Soutto M, Davis GM, McLoed AG, Townsend MJ, Glimcher LH, Mortlock DP, Aune TM
J Immunol. 2010 185 (3): 1492-501

PMID: 20574006 · PMCID: PMC2923829 · DOI:10.4049/jimmunol.1000124

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 bacterial artificial chromosome 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 in NK cells. This distal regulatory element is a Runx3 binding site in Th1 cells and is needed for RNA polymerase II recruitment to IFNG, but it is not absolutely required for histone acetylation of the IFNG locus. These results support a model whereby IFNG uses cis-regulatory elements with cell type-restricted function.

MeSH Terms (20)

Animals Cell Lineage Cells, Cultured Conserved Sequence Core Binding Factor Alpha 3 Subunit Gene Expression Regulation Genetic Loci Humans Interferon-gamma Killer Cells, Natural Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Natural Killer T-Cells Protein Transport Regulatory Elements, Transcriptional RNA Polymerase II Th1 Cells Transcription Initiation Site

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