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It has been suggested that hypomethylation of the \u22121500\/\u22121100 domain of the 5\u2032 flanking regulatory region of the rat glial fibrillary acidic protein gene may be specific for neuroectodermal derivatives such as neurons and astrocytes. In the present work the methylation status of one of those seven CG sites (the \u22121176) of the \u2018neuroectoderm\u2010specific domain\u2019 was analyzed. In agreement with the neuroectoderm hypothesis, the \u22121176 site is highly demethylated in astroglial, oligodendroglial and neuronal cells, but heavily methylated in microglial and fibroblast cells. The three different glial population are derived from the same tissue (cerebral hemispheres of newborn rats) but have a different embryological origin: oligodendrocytes and astrocytes originate from neuroectoderm, while microglia is of mesodermal origin.<\/jats:p><jats:p>It is not clear if <jats:italic>GFAP<\/jats:italic>\u2010negative neuronal cells maintain such demethylation in the advanced stage of maturation or if they undergo a second phase of <jats:italic>de novo<\/jats:italic> methylation. In order to clarify this point we used a subcellular fractionation method which allowed us to separate two different nuclear populations from adult rat cerebral hemispheres: one enriched in neuronal nuclei (called N1) and the other enriched in glial nuclei (N2). A higher methylation level of the \u22121176 site was detected in the N1 fraction, suggesting the <jats:italic>GFAP<\/jats:italic> gene undergo a <jats:italic>de novo<\/jats:italic> methylation process during neuronal maturation. This observation is in agreement with recent results showing a <jats:italic>de novo<\/jats:italic> methylation of the \u22121176 site during postnatal brain development. We hypothesize that a DNA demethylation process takes place in neuroectodermal precursor cells and that the \u22121176 site persists demethylated at the earlier stages of neuronal differentiation (immature neurons) and becomes fully methylated at more advanced stages of differentiation.<\/jats:p><\/jats:sec>","DOI":"10.1016\/s0736-5748(99)00059-3","type":"journal-article","created":{"date-parts":[[2002,7,25]],"date-time":"2002-07-25T15:07:39Z","timestamp":1027609659000},"page":"821-828","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<i>GFAP<\/i> gene methylation in different neural cell types from rat brain"],"prefix":"10.1002","volume":"17","author":[{"given":"V.","family":"Barresi","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Facolt\u00e0 di Medicina Universit\u00e0 di Catania Viale A. 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