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However, there are no direct analyses of human brain tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunohistochemical detection of global epigenetic markers was performed on temporal lobe samples of autopsied fetuses and infants with documented <jats:styled-content style=\"fixed-case\">PNAE<\/jats:styled-content>. They were compared to age\u2010, sex\u2010, and postmortem delay\u2010matched control cases (18 pairs; 20 to 70.5\u00a0weeks postconception). Temporal lobe tissue from a macaque monkey model of <jats:styled-content style=\"fixed-case\">PNAE<\/jats:styled-content> was also studied (5.7 to 6\u00a0months of age). We used antibodies targeting 4 <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> cytosine, 4 histone methylation, and 6 histone acetylation modifications and assigned scores based upon the semiquantitatively graded intensity and proportion of positively labeled nuclei in the ventricular and subventricular zones, ependyma, temporal cortex, temporal white matter, dentate gyrus (DG), and CA1 pyramidal layer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Temporal changes were identified for almost all marks according to the state of maturation in the human brain. In the DG (and 3 other brain regions), a statistically significant increase in H3K9ac was associated with <jats:styled-content style=\"fixed-case\">PNAE<\/jats:styled-content>. Statistically significant decreases were seen among 5mC, H3K4me3, H3K9ac, H3K27ac, H4K12ac, and H4K16ac in select regions. In the macaques, H3K36me3 decreased in the DG, and the ependyma showed decreases in 5fC and H3K36me3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In human brain, global intranuclear epigenetic modifications are brain region and maturation state\u2010specific. These exploratory results support the general hypothesis that <jats:styled-content style=\"fixed-case\">PNAE<\/jats:styled-content> is associated with a global decrease in <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation, a global decrease in histone methylation, and a global increase in histone acetylation. Although the human and monkey subjects are not directly comparable in terms of brain maturation, considering the rapid temporal changes in global epigenetic modifications during brain development, interspecies comparisons may be extremely difficult.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14052","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T15:01:05Z","timestamp":1557500465000},"page":"1145-1162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Global DNA Methylation and Histone Posttranslational Modifications in Human and Nonhuman Primate Brain in Association with Prenatal Alcohol Exposure"],"prefix":"10.1111","volume":"43","author":[{"given":"Jessica S.","family":"Jarmasz","sequence":"first","affiliation":[{"name":"Department of Pathology University of Manitoba Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Stirton","sequence":"additional","affiliation":[{"name":"Max Rady College of Medicine University of Manitoba Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duaa","family":"Basalah","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Manitoba Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Davie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics University of Manitoba Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling K.","family":"Clarren","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Washington School of Medicine Seattle Washington USA"},{"name":"Department of Pediatrics University of British Columbia Faculty of Medicine 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