Distal regions of the human IFNG locus direct cell type-specific expression.
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.
Collins
Patrick L
PL
Division of Rheumatology, Department of Medicine, Medical Center North T3219, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN 37232, USA.
Chang
Shaojing
S
Henderson
Melodie
M
Soutto
Mohammed
M
Davis
Georgia M
GM
McLoed
Allyson G
AG
Townsend
Michael J
MJ
Glimcher
Laurie H
LH
Mortlock
Douglas P
DP
Aune
Thomas M
TM
D000818:Animals; D019070:Cell Lineage / Q000235:genetics* / Q000276:immunology*; D002478:Cells, Cultured; D017124:Conserved Sequence / Q000235:genetics / Q000276:immunology; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D056426:Genetic Loci / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics*; D007694:Killer Cells, Natural / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D012319:RNA Polymerase II / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000276:immunology; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D024363:Transcription Initiation Site
D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human; D007371:Interferon-gamma; D012319:RNA Polymerase II