Fig. 1

a Impaired larval T cell development in mutant fish. Diagnostic whole-mount RNA in situ hybridization pattern ²³in wild-type and dnmt1 mutant fish at 5 dpf using rag1 (thymus encircled in black), and gh (hypophysis encircled in blue) specific probes (left panel); hybridization pattern for foxn1, a marker of thymic epithelium^59,60 (right panel). Scale bar, 100 μm. Panels are representative of 25 animals each. b Schematic of functional domains in the dnmt1 protein (not to scale); NLS, nuclear localization signal; RFTS, replication foci targeting site; CXXC, cysteine-rich domain; BAH, bromo-adjacent homology domains 1 and 2; MTase, catalytic domain. Arrow, approximate position of the amino acid replacement in the target recognition domain, TRD. c The asparagine residue mutated in the dnmt1^t25501 allele occurs in an evolutionarily conserved region of the enzyme. d In the structure of the mouse Dnmt1 protein in complex with a hemi-methylated substrate, close apposition of the mutated asparagine residue to the substrate DNA in the catalytic site is observed²⁶ (PDB ID: 4DA4). e, f Hypomethylation of cytosine residues in CpG dinucleotides of DNA extracted from whole body of 18 dpf larvae (e) (n = 3) and sperm of adult homozygous mutants (f) (n = 3). In (e) and (f), density refers to the fraction of CG sites with a particular methylation ratio. g Mean methylation levels of CG dinucleotides for DNAs shown in (e) and (f). Values shown represent mean ± mad; n = 3. Source data are provided as Source Data file.