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. 2019 Oct 1;10:907. doi: 10.3389/fgene.2019.00907

Figure 5.

Figure 5

Epigenetic delay of autism-associated DML. (A) Relationship between male fetal brain tissue specimens at four stages of development (days postconception, d.p.c.) and postmortem brain tissue from the subventricular zone (SVZ), prefrontal cortex (PFC), temporal cortex (TC), and cerebellum (CB) regions of typically developing (green) and autism-diagnosed (orange) specimens. Correlation matrix showing Pearson correlation coefficient and significance of relationship (P < 0.001); X denotes nonsignificant. (B) Scatterplot of relationship of typically developing control (green) and autism (orange) methylation states at epigenetically dynamic regions versus male fetal brain methylation states from 23 days to 184 d.p.c. for SVZ, PFC, TC, and CB regions. (C) Scaled chromosomal view of location of DML in the ISLR2 gene. CpG island region indicated in green; bivalent domain indicated by H3K4me3 (light blue) and H3K27me3 (pink). Location of all 450k probes indicated in black and location of DML indicated in red. Yellow highlighted region shows DML overlaps with splicing event of exon. (D) DNA methylation at one CpG site on the 450k array within the EDR of ISLR2 progressively increased from low (∼18%) to intermediate (∼40%) levels during fetal brain development and in postnatal SVZ of typically developing control brain. The methylation level at this site in the SVZ from ASD cases remained low (∼30%; ASD young cases), resembling that of fetal brain tissue at 109–184 d.p.c. (E) Scaled chromosomal view of location of DML in the SOCS2 gene. CpG island region indicated in green; bivalent domain indicated by H3K4me3 (light blue) and H3K27me3 (pink). Location of all 450k probes indicated in black and location of DML indicated in red. Yellow highlighted region shows DML overlaps with splicing event of exon. (F) DNA methylation level at one CpG site on the 450k array within the EDR of SOCS2 increased from ∼20 to ∼65% pre- to postnatally in normal brain, while it remained at ∼40–50% in postnatal SVZ of ASD cases. *, denotes significant methylation difference at P < 0.05 between control and autism samples.