A recently identified and previously unknown function for the protein chromobox protein-7 (CBX7) indicates that it acts not only as a gene repressor but also as a key promoter of gene activation and inflammatory signaling in immune cells. Investigators shared the discovery in the paper, “CBX7 Functions as a Methylation-Dependent Inducer of Gene Transcription and Regulator of Cytosolic Signaling in Lymphoid Cells,” recently published in the journal, Science Advances.
According to researchers at National Jewish Health in Denver, the discovery could open new avenues for treating asthma and other allergic diseases. CBX7 has long been recognized for its role in suppressing gene expression, they noted. However, the new study found that CBX7 can form a methylation-dependent transcriptional complex that activates gene transcription by binding directly to cytokine gene promoters, a finding that challenges conventional understanding of the protein’s function.
Investigators also discovered that CBX7 moves from the cell nucleus into the cytosol, where it assembles a methylation-dependent signaling complex involving c-Raf, MEK1/2 and CK2-α. This complex generates and sustains ERK1/2 signaling, a pathway known to regulate immune responses and inflammation, they wrote.
More importantly, investigators reported finding that CBX7 is induced by allergens and plays an essential role in cytokine production in both mouse immune cells and lymphoid cells obtained from asthma patients. Through genetic and pharmacological experiments, researchers demonstrated that CBX7 is required for the development of allergic asthma in multiple mouse models.
As part of the study, RNA sequencing analyses further highlighted the protein’s broad influence on immune function. T cells lacking CBX7 showed widespread changes in gene expression, the authors noted, with major decreases in pathways associated with cytokine signaling, asthma and T-helper cell differentiation.
Notably, researchers observed that CBX7-mediated transcriptional activation and ERK1/2 signaling were specific to lymphoid cells and were absent in epithelial cells, which they said suggested a specialized role in immune regulation.
Researchers emphasized the potential this discovery has in developing a potential target for future therapies aimed at controlling allergic diseases and asthma.
