ArticleFunctional & integrative genomics2025
Multi-Omics analysis unveils the regulatory mechanism of ZNF423 in bovine intramuscular fat formation.
Article in Functional & integrative genomics, 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
Marbling (intramuscular fat) is a crucial determinant of beef palatability. Zinc finger protein 423 (ZNF423) plays a key role in adipocyte differentiation and lipid metabolism, but its regulatory mechanisms, particularly in bovine adipocytes, remain poorly understood. This study demonstrates that si-ZNF423 inhibits adipocyte proliferation by disrupting the G1/S transition and down-regulating key proliferation markers. Additionally, ZNF423 knockdown suppresses the expression of major adipogenic transcription factors (PPARγ, C/EBPβ) and lipid metabolism genes (SCD1, FABP4), resulting in reduced triglyceride (TG) accumulation and impaired lipid droplet formation. Transcriptomic and non-targeted metabolomic analyses indicated that ZNF423 regulates adipogenesis through pathways involving retinoic acid (RA) signaling. ChIP and dual luciferase assays confirmed that ZNF423 directly binds to the promoters of SLC45A2 and SNCG, identifying these genes as novel downstream targets. Notably, RA treatment compensates for the effects of si-ZNF423 knockdown, not only restoring and significantly enhancing ZNF423 activity and downstream adipogenic processes, highlighting a conserved interplay between ZNF423 and RA signaling in bovine adipogenesis. This study provides new insights into the molecular mechanisms of bovine fat development, offering potential targets for improving beef quality.
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