Figure 3.

Transcriptome analysis of neuron-like PHF6 KO cells. (a) Heatmap displaying 1,338 deregulated genes between differentiated SK-N-BE (2) PHF6 KO and control cells with adjusted p value < 0.05 (FDR corrected). 626 genes were upregulated, and 712 were downregulated in PHF6 KO cells. Heatmap was created using the pheatmap package v.1.0.12⁸⁶ applying the standard settings (complete linkage method for hierarchical clustering for both columns and rows, scaling for rows). Blue = downregulated; red = upregulated. (b,c) Gene Ontology (GO) term analysis of (b) upregulated and (c) downregulated genes depicting the top five GO terms for biological processes. (d) Comparison of deregulated genes after KO/KD of common chromatin remodelers and transcription factors with deregulated genes after PHF6 KO divided in up- and downregulated genes. Deregulated genes after KO/KD of either KDM5C (Kdm5c KO mouse model, RNA sequencing of amygdala and frontal cortex)³⁶, the BAF complex (dKO Baf155/Baf170 mouse model, RNA sequencing of the pallium of E17.5 embryos)³⁷, BMI1 (Bmi1 KO mouse model, RNA sequencing of whole brain)³⁸ or TCF4 (TCF4 KD SH-SY5Y neuroblastoma cells)³⁹ expressed a highly significant overlap with up- and downregulated genes after PHF6 KO. Darkness of color correlates with significance. (e) Significant GO terms involved in neuron development and axonogenesis (p < 0.005). (f) Venn diagram depicting that deregulated genes were significantly enriched for genes implicated in neurodevelopmental disorders (NDDs). Asterisks indicate statistical significance (*p < 0.05, **p < 0.01, ***p < 0.001).