Figure 4. Translational and transcriptional co-regulation connects developmentally distinct ASD-affected modules.
(A) Co-expression based network plot of FMRP interactions with genes in M2, M16, and M17 that are either affected by RDNVs or in an ASD candidate list. Genes are plotted as in Figure 2 and 3, but now across modules, with FMRP placed at the center.
(B) Summary of TF binding site (TFBS) enrichment in modules for TFs that have evidence for function in a neurodevelopmental context. Dashed lines indicate enrichment in the module for predicted binding sites.
(C-G) MEF2A, MEF2C, SATB1, FOXO1, and ELF1 are all enriched for their binding motifs in the upstream regions of ASD gene-enriched modules following anti-correlated developmental patterns. Network plots highlight genes with a predicted binding site (light dashed arrow) contributing to this enrichment that are also affected by RDNVs or in an ASD candidate list. Arrows representing a TFBS found in a ChIP experiment are marked in dark blue.
For network plots, the top 1000 positive connections between genes are plotted and node size is proportional to connectivity within the genes' assigned module, therefore larger nodes are more central hubs. See also Table S3.