Extended Data Fig. 5: 3D conformation changes at the Fgf8 locus.
a, Sequences of the 6 CTCFs binding sites detected in the MusD-Dac1J as identified with the FIMO (Find Individual Motif Occurrences) suite. The program uses a dynamic programming algorithm to convert log-odds scores into p-values, assuming a zero-order background model. p-value < 10−4 is considered as significant and marked in bold. FIMO score and p-value are indicated for each binding site. Orange and red triangles represent sense and antisense CTCF sites respectively. b, Zoom-in from the Capture-Hi-C subtraction map between wild-type and Dac1J/Dac1J (129s2/Sv) in Fig. 3d showing the Fgf8 TAD. c, Capture-Hi-C of the Lbx1/Fgf8 locus (mm10, chr19: 45,100,000-45,900,000) from Dac1J-Bl6 E11.5 mouse limbs buds. Data show the c-HiC as merged signals of n = 2 biological and 2 technical replicates. Subtraction maps between mutants and wild-type show gain (red) and loss (blue) of interaction in the mutant compared to the wild-type. d, CTCF ChIP-sequencing from forelimbs at E10.5 and E11.5 showing tracks at the Fgf8 locus. e, CpG DNA methylation status of 19 CpGs in the MusD-Dac1J 5’LTR from E11.5 Dac1J/Dac1J (129s2/Sv) hearts (left) and E11.5 5’LTR-LacZ KI/WT limbs (right). f, Skeletal analysis of E18.5 5LTR-LacZ KI +/- forelimbs stained with alcian blue (cartilage) and alizarin red (bone). Scale bars 1 mm, n = 8/8 show a similar phenotype.
