Fig. 2: MSL2 regulates haploinsufficient genes.
a, k-means clustering of bi-to-mono genes (log2[FC] < −2) across male CaBl and BlCa and female CaBl and 9sCa NPCs based on allele-specific log2[FC] (Supplementary Table 2). The coloured bars indicate 14 subclusters. b, Haploinsufficiency scores (left) and triplosensitivity (right)3 of bi-to-mono genes in four NPCs (as described in a). Left, the dot size and colour represent haploinsufficiency scores and the presence (red) and absence (blue) of triplosensitivity. Associations with selected human diseases from ClinGen45 are shown. An expanded version is shown in Extended Data Fig. 4b. c, The overlap of bi-to-mono genes in male CaBl and BlCa and female CaBl and 9sCa NPCs, with the indicated classes of published monoallelic genes (Supplementary Tables 4–6). Unknown, previously unidentified as monoallelic genes. P values indicate significance for bi-to-mono gene enrichment in published datasets calculated using two-sided Fisher’s exact tests. d, Allelic differential expression changes (log2[FC] (Msl2 KO/WT) in allele 1 and allele 2) for bi-to-mono genes consistent in male CaBl and BlCa (left) or female CaBl and 9sCa (right) NPCs. M, maternal; P, paternal. e, Schematic and RNA-seq tracks of Slc38a1 in male CaBl and BlCa and Decr1 in female CaBl and 9sCa WT and Msl2-KO NPCs. f, Allelic differential expression changes (log2[FC] (Msl2KO/WT) in allele 1 and allele 2) for bi-to-mono genes consistent in male and female CaBl (left) and male BlCa and female 9sCa (right) NPCs. g, Schematic and RNA-seq tracks of Skida1 in male and female CaBl WT and Msl2-KO NPCs, and Slc38a3 in male and female BlCa and 9sCa WT and Msl2-KO NPCs. h, Allelic differential expression changes (log2[FC] (Msl2KO/WT)) for all XCI escapees in female 9sCa (left) and CaBl (right) NPCs. The grey lines indicate the log2[FC] = −2 threshold. All escapees are summarized in Supplementary Table 7. i, Allelic expression of escapees with bi-to-mono changes in WT and Msl2-KO 9sCa and CaBl NPCs. For d, f and h, the diagrams were created using BioRender.
