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

Peng Li1, Sree Pulugulla2, Sonali Das2

  • 1Amgen Inc, Rockville, United States.

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|January 9, 2025
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Summary

A new screening pipeline called SPICE can predict transcription factor binding partners and DNA motif spacing. This method identified novel JUN-IKZF1 interactions, revealing a new role for IKZF1 in regulating IL10 gene expression.

Keywords:
AP1IKZF1IL-10IL-21JUNProtein-DNASPICEcomputational biologyimmunologyinflammationmousesystems biology

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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.