ArticleScientific reports2025
Characterization of a cis-regulatory element upstream of matrix metalloproteinase-9.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Dysregulated enhancer activity disrupts gene expression, contributing to disease. However, the structural and functional complexity of enhancers hinders their characterization. Here, we investigate a cis-regulatory element upstream of matrix metalloproteinase-9 (MMP9), a gene implicated in cancer, cardiovascular disease, inflammation, and pregnancy complications. Using luciferase assays and CRISPR-Cas9 mediated knockout in a human placental cell line, we define a one kilobase segment that enhances MMP9 expression. Further dissection reveals two activating sub-segments and, unexpectedly, one repressive sub-segment. Molecular assays suggest transcription factors that mediate these opposing effects. This work adds to the growing understanding that enhancers can integrate both activation and repression, revealing a more complex regulatory architecture than previously appreciated. Together, these findings underscore the importance of enhancer dissection for understanding gene regulation across tissues and diseases.
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