GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307505/primaryOK200Methylation profilingDanio rerio Homo sapiensMethylation profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307505GEOGSEfalseFINE-EM-seq: a rapid isothermal amplification method enabling comprehensive methylome profiling of zebrafish early embryosDNA methylation plays a crucial role in development and disease. Bisulfite-free methods such as enzymatic methyl sequencing (EM-seq) offer gentle approaches for whole-genome analysis, but they typically depend on PCR-based library amplification, which distorts coverage and methylation quantification. Here, we introduce FINE (Fast Isothermal amplification via Nicking Enzyme), a robust isothermal amplification strategy that leverages a nicking enzyme-assisted strand displacement reaction and can amplify methylation libraries from sub-nanogram inputs in 20 minutes. FINE-EM-seq increases library efficiency and coverage uniformity compared to PCR-based approaches, minimizing amplification bias and improving methylation calling accuracy. Applied to zebrafish embryos at four early developmental stages, FINE-EM-seq characterized stage-associated methylation dynamics through blastulation and early gastrulation. Furthermore, our analysis revealed blastulation-associated differentially methylated regions (DMRs) overlapping with AT-rich regions that were previously under-covered. These results illustrate that FINE-EM-seq is a rapid, robust solution for low-input whole-genome methylation sequencing with broad utility in developmental biology and clinical epigenomics.2026/04/09GSE307505GSM9225697GSM9225696GSM9225695GSM9590057GSM9590058GSM9590055GSM9590056GSM9590053GSM9225711GSM9590054GSM9225710GSM9225699GSM9225698GSM9225709GSM9225708GSM9225707GSM9225706GSM9590060GSM9590061GSM9225705GSM9225704GSM9225703GSM9590066GSM9225702GSM9590064GSM9225701GSM9225700GSM9590065GSM9590062GSM9590063GSM95900593469334281307505Danio rerio Homo sapiens[42058509]