Review of PU.1 and IRF8 Synergy in Chromatin Regulation during Monocyte-to-Macrophage Differentiation

Abstract Background: The differentiation of monocytes into macrophages is a fundamental process in immune response, governed by various transcription factors, notably PU.1 and IRF8. While both transcription factors have well-established individual roles in chromatin remodeling and gene expression, the precise nature of their cooperative interactions during monocyte-to-macrophage differentiation remains incompletely understood. Methods: A systematic review was conducted following PRISMA guidelines. Studies published between 2015 and 2025 were identified through PubMed, Google Scholar, and Scopus, using keywords such as "PU.1," "IRF8," "chromatin remodeling," and "macrophage differentiation." Studies focusing on experimental approaches like ChIP-sequencing, gene expression profiling, and histone modification were included. Data extraction was performed, and findings were synthesized to assess the roles of PU.1 and IRF8 in macrophage differentiation. Results: This review identifies key findings on the synergistic interaction between PU.1 and IRF8, emphasizing their pivotal roles in modulating chromatin dynamics, enhancing macrophage-specific gene expression, and regulating immune responses. The studies reviewed highlight the impact of these transcription factors on chromatin accessibility and gene activation critical to macrophage differentiation. Conclusions: PU.1 and IRF8 function together to regulate key aspects of macrophage differentiation, with potential therapeutic implications for diseases involving macrophage dysfunction, including chronic inflammation, autoimmune disorders, and cancer. The insights presented here contribute to a deeper understanding of macrophage biology and offer directions for future research aimed at exploiting these transcription factors in therapeutic interventions.