A new pipeline SPICE identifies novel JUN-IKZF1 composite elements

Authors

• D Stavreva
• K Wagh
• L Hoang
• G Hager
• A Upadhyaya
• R Chari
• L Schiltz

Abstract

Transcription factor partners can cooperatively bind to DNA composite elements to augment gene transcription. Here, we report a novel protein-DNA binding screening pipeline, termed Spacing Preference Identification of Composite Elements (SPICE), that can systematically predict novel protein binding partners and their DNA motif spacing preferences. SPICE not only successfully de novo predicted known composite elements, including AP1-IRF composite elements (AICE) and STAT5 tetramers, but also predicted a range of potential novel binding partners, including JUN-IKZF1 composite elements throughout the genome. We showed cooperative binding of JUN and IKZF1 to an upstream conserved noncoding region, CNS9, in the human IL10 gene. Furthermore, the activity of an IL10 luciferase reporter construct depended on both AP1 and IKZF1 binding sites within this composite element in primary mouse B cells and T cells. These data provide new insights into the biological actions of IKZF1 and AP1 and moreover establish SPICE as a valuable new pipeline for predicting novel transcription binding complexes that regulate gene transcription.

Scientific Focus Area: Immunology

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