{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:53:27Z","timestamp":1792144407234,"version":"4.4.0"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,4,14]],"date-time":"2019-04-14T00:00:00Z","timestamp":1555200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant 2016-06035 to MR, International Rett Syndrome Foundation (IRSF) grant #3212 to MR, and Ontario Rett Syndrome Association to MR","award":["IRSF 3212, NSERC-DG2016-06035"],"award-info":[{"award-number":["IRSF 3212, NSERC-DG2016-06035"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Methyl CpG binding protein-2 (MeCP2) isoforms (E1 and E2) are important epigenetic regulators in brain cells. Accordingly, MeCP2 loss- or gain-of-function mutation causes neurodevelopmental disorders, including Rett syndrome (RTT), MECP2 duplication syndrome (MDS), and autism spectrum disorders (ASD). Within different types of brain cells, highest MeCP2 levels are detected in neurons and the lowest in astrocytes. However, our current knowledge of Mecp2\/MeCP2 regulatory mechanisms remains largely elusive. It appears that there is a sex-dependent effect in X-linked MeCP2-associated disorders, as RTT primarily affects females, whereas MDS is found almost exclusively in males. This suggests that Mecp2 expression levels in brain cells might be sex-dependent. Here, we investigated the sex- and cell type-specific expression of Mecp2 isoforms in male and female primary neurons and astrocytes isolated from the murine forebrain. Previously, we reported that DNA methylation of six Mecp2 regulatory elements correlated with Mecp2 levels in the brain. We now show that in male brain cells, DNA methylation is significantly correlated with the transcript expression of these two isoforms. We show that both Mecp2 isoforms are highly expressed in male neurons compared to male astrocytes, with Mecp2e1 expressed at higher levels than Mecp2e2. Our data indicate that higher DNA methylation at the Mecp2 regulatory element(s) is associated with lower levels of Mecp2 isoforms in male astrocytes compared to male neurons.<\/jats:p>","DOI":"10.3390\/ijms20081845","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T11:15:58Z","timestamp":1555326958000},"page":"1845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["DNA Methylation Contributes to the Differential Expression Levels of Mecp2 in Male Mice Neurons and Astrocytes"],"prefix":"10.3390","volume":"20","author":[{"given":"Vichithra R.B.","family":"Liyanage","sequence":"first","affiliation":[{"name":"Regenerative Medicine Program, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl O.","family":"Olson","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robby M.","family":"Zachariah","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Davie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-6116","authenticated-orcid":false,"given":"Mojgan","family":"Rastegar","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"415825","DOI":"10.1155\/2012\/415825","article-title":"Linking epigenetics to human disease and Rett syndrome: The emerging novel and challenging concepts in MeCP2 research","volume":"2012","author":"Zachariah","year":"2012","journal-title":"Neural Plast."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1086\/302690","article-title":"Rett syndrome and beyond: Recurrent spontaneous and familial MECP2 mutations at CpG hotspots","volume":"65","author":"Wan","year":"1999","journal-title":"Am. 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