The two interfaces of the STAT1 N-terminus exhibit opposite functions in IFNγ-regulated gene expression

• Four surfaced exposed and negatively charged amino acid residues in the N-terminal domain of STAT1 are engaged in the release of tyrosine-phosphorylated tetramers from DNA. • Despite elevated tyrosine-phosphorylation and prolonged nuclear accumulation upon stimulation of cells with IFNγ, the trans...
Ausführliche Beschreibung

• Four surfaced exposed and negatively charged amino acid residues in the N-terminal domain of STAT1 are engaged in the release of tyrosine-phosphorylated tetramers from DNA. • Despite elevated tyrosine-phosphorylation and prolonged nuclear accumulation upon stimulation of cells with IFNγ, the transcriptional consequences of STAT1 N-terminal gain-of-function mutants affect gene expression not globally, but in a promoter-specific manner. • The STAT1 N-domain is involved in the termination of IFNγ-mediated signal transduction by disrupting higher-order oligomers on DNA. • Our findings reveal a new mechanistic insight into how protein-DNA interactions regulate STAT1-mediated target gene recognition. Ausführliche Beschreibung