A new pipeline SPICE identifies novel JUN-IKZF1 composite elements.

Area of Science:

• Molecular Biology
• Genomics
• Bioinformatics

Background:

• Transcription factors bind DNA cooperatively to regulate gene transcription.
• Identifying these interactions and their DNA binding preferences is crucial for understanding gene regulation.

Purpose of the Study:

• To develop a novel screening pipeline, SPICE, for systematically predicting protein-DNA binding partners and motif spacing.
• To identify novel transcription factor binding complexes and their regulatory roles.

Main Methods:

• Developed and utilized the Spacing Preference Identification of Composite Elements (SPICE) pipeline.
• Applied SPICE to identify known and novel composite elements, including AP1-IRF composite elements (AICEs) and STAT5 tetramers.
• Investigated the novel JUN-IKZF1 interaction at the human IL10 gene's CNS9 region.

Main Results:

• SPICE successfully identified known composite elements and uncovered novel partners like JUN-IKZF1.
• A non-canonical IKZF1 binding site was found in the IL10 gene's CNS9 region.
• Cooperative binding of JUN and IKZF1 was confirmed, regulating IL10 reporter gene activity in B and T cells.

Conclusions:

• The study reveals an unappreciated global association between IKZF1 and AP1 transcription factors.
• SPICE is established as a valuable tool for discovering novel transcription factor binding complexes.
• The findings highlight a new regulatory mechanism for the IL10 gene involving JUN and IKZF1.