FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs

Area of Science:

• Molecular Biology
• Cancer Biology
• Epigenetics

Background:

• Focal adhesion kinase (FAK) is overexpressed in many cancers and can translocate to the nucleus.
• In the nucleus, FAK regulates transcription factors, but the mechanisms are largely unknown.
• FAK's role in controlling gene expression, particularly in cancer, requires further elucidation.

Purpose of the Study:

• To investigate the mechanisms by which nuclear FAK controls gene expression.
• To determine if FAK influences chromatin accessibility.
• To identify FAK-regulated genes involved in anti-tumor immunity.

Main Methods:

• Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) to assess chromatin accessibility.
• RNA sequencing (RNA-seq) to analyze gene expression.
• Analysis of transcription factor binding motifs and protein-DNA interactions.

Main Results:

• FAK was found to control chromatin accessibility at specific target genes.
• FAK-dependent chromatin accessibility correlated with differential gene expression.
• The study identified interleukin-33 (Il33) as a FAK-regulated gene critical for anti-tumor immunity.
• c-Jun, a component of AP-1, was shown to regulate Il33 expression via FAK-dependent enhancer binding.

Conclusions:

• FAK controls gene transcription through modulation of chromatin accessibility, representing a novel mechanism for nuclear FAK function.
• This finding provides new insights into how FAK regulates gene expression, impacting processes like anti-tumor immunity.
• The study highlights a potential therapeutic target for manipulating FAK-driven gene expression in cancer.