Pervasive chromatin remodeling at X-inactivation escape genes in schizophrenic males

Reanalyzing a large methylome dataset of 225 schizophrenic and 450 control samples derived from the prefrontal cortex revealed that 6 male patients have predominantly hypomethylated probes mostly on chromosome X, affecting the same genes in all six. Network analysis of the differentially methylated genes revealed a dense network of transcription factors, histone and chromatin remodeling proteins, with 15 of the X-located genes expressed at the synapse, including NLGN4X, SYN1 and MECP2. Mapping a recent experimental dataset of G-quadruplexes (G4s) onto the differentially methylated probes revealed that the probes in the group of six overlapping with G4s on chromosome X are significantly more hypomethylated than non-overlapping and non-X probes whereas in the rest of the patients G4-overlapping probes are more methylated than non-overlapping ones, revealing a distinct pathology, involving chromatin remodeling for the six patients. Unexpectedly, the hypomethylated genes in them significantly overlapped with gene locations where X-inactivation escapism was observed in women.