Fig 2: Molecular profiling of Ohiam/m brain tissue with integration of genome-wide methylome with RNAseq and Sap130 ChIPseq analyzes.A Increased methylation of CpG sites in a DMR found in Klf17 in the Ohiam/m brain tissue. B Venn diagrams show two-way intersection of downregulated DEGs with genes associated with DMR and three-way intersection of down regulated DEGs, genes associated with DMR, and genes recovered from Sap130 ChiPSeq. C, D ToppGene enrichment analysis for Mouse Phenotypes (C) and Diseases (D) recovered from the two-way intersection of the downregulated DEGs with genes associated with DMRs.

Fig 3: Sap130 chromatin immunoprecipitation sequencing analysis of mouse brain and examination of cilia in the Ohia brain tissue.A Sap130 occupancy in the 5’ upstream promoter region of selected genes. B Motif enrichment analysis of the Sap130 ChIPseq target genes identified putative Sap130 DNA binding sequences. C–F Pathways in GO Biological Process (C) and Cellular Components (D), as well as Human Phenotype (E), and Disease (F) terms recovered from ToppGene gene enrichment analysis of Sap130 ChIPseq target genes. G–I Cilia visualization in sections of wildtype (G) and Ohiam/m mutant brain tissue (H) immunostained with Arl13b (cilia, green), γ-tub (centrosome, red) and DAPI. Quantification showed reduction of cilia in the mutant brain (I, n = 3 Ohia mutant and 4 littermate controls). The graph represents the mean ± SD, with P = 0.0274 determined by 2-tailed, unpaired t-test. Magnification in panels G and H are the same, with scale bar = 200 µm. Source data are provided as a Source Data file.

Fig 4: Emx1-cre Sap130f/− mice show microcephaly with transcriptome profiling showing abnormal neurodevelopment.A Wildtype newborn control (left) and Emx1-cre Sap130f/− mutant (right) brains. Scale bar = 500 µm. B Brain/body weight ratio for newborn control (n = 18) and Emx1-cre Sap130f/− (n = 6) mice confirm brain hypoplasia in the Emx1-cre Sap130f/− mice. C qPCR of Sap130 transcripts in E14.5 forebrain tissue from 4 control and 4 Emx1-cre Sap130f/− mice showed decrease in Sap130 transcripts, demonstrating efficacy of the Emx1-Cre mediated Sap130 deletion. The graph represents the mean ± SD, with P = 0.0108 determined by 2-tailed, unpaired t-test. D qPCR of Wdr62 transcripts in E14.5 forebrain tissue from 4 control and 4 Emx1-cre Sap130f/− mice showed increase transcript expression, indicating possible centrosome amplification. The graph represents the mean ± SD, with P = 0.0307 determined by 2-tailed, unpaired t-test. E–H IPA and ToppGene analysis of DEGs from RNAseq of E14.5 forebrain tissue from Emx1-cre Sap130f/− vs. control mice. Shown are the results obtained with IPA Canonical Pathway analysis (E), Gene Set analysis (F) for hallmark centrosome, hypoxia, and mitotic spindle genes, and ToppGene analysis for Mouse Phenotype (G) and Disease (H). Source data are provided as a Source Data file.