Global landscape of mouse and human cytokine transcriptional regulation

Area of Science:

• Immunology
• Molecular Biology
• Bioinformatics

Background:

• Cytokines are crucial cell-signaling proteins in immunity and disease.
• Their expression is tightly controlled by transcription factors (TFs) at the transcriptional level.

Purpose of the Study:

• To create a comprehensive database (CytReg) of TF-cytokine gene interactions.
• To elucidate general principles governing cytokine gene transcriptional regulation.
• To provide a resource for predicting TF-disease associations and identifying regulatory axes in autoimmune diseases.

Main Methods:

• Compiled TF-cytokine gene interaction data from three decades of research into the CytReg database.
• Integrated CytReg with functional datasets to analyze regulatory principles.
• Utilized co-expression and motif analyses for predicting novel interactions, followed by experimental validation.

Main Results:

• CytReg contains 843 human and 647 mouse TF-cytokine gene interactions.
• Demonstrated a correlation between TF connectivity and immune phenotype/disease.
• Identified the balance between tissue-specific and pathogen-activated TFs in cytokine regulation.
• Showcased cooperativity and plasticity in cytokine gene regulation.

Conclusions:

• CytReg serves as a valuable framework for understanding cytokine gene regulation.
• The database facilitates prediction of TF-disease associations and identification of regulatory pathways in autoimmune conditions.
• Highlights research biases and provides a resource for future experimental studies in cytokine regulation.