The isolation of brain nuclei prior to the flow cytometry separation was performed mostly as previously described in Kozlenkov et al. (Sci Adv. 2018). Tissue (~300 mg) was homogenized in ice-cold lysis buffer (320 mM sucrose, 5 mM CaCl2, 3 mM Mg(Ac)2, 0.1 mM EDTA, 0.1% Triton X-100, 1 mM DTT, 0.1 mM benzamidine, 0.1 mM phenylmethylsulfonyl fluoride (PMSF), and 10mM Tris-HCl, pH 8.0), underlaid with the sucrose buffer (1.8 M Sucrose, 3 mM Mg(Ac)2, 1 mM DTT, and 10 mM Tris-HCl pH 8.0), and centrifuged for 1h at 24,000 rpm. The nuclear pellets were then resuspended in the antibody-incubation buffer (0.5% BSA, 3mM MgCl2, and 10 mM Tris-HCl, pH 8.0) and incubated with antibodies against NeuN, SOX10 and IRF5 for 1 hr at 4°C. Fluorescence-activated nuclei sorting (FANS) was then used to isolate neurons (NeuN+SOX10- population), oligodendrocyte lineage cells (NeuN-SOX10+ population), consisting of mature oligodendrocytes and a smaller population of OPCs, microglia (NeuN-SOX10-IRF5+ population) and the remaining population (NeuN-SOX10-IRF5-) that mostly consisted of astrocytes. Alexa488-conjugated anti-NeuN antibodies (1:1000 dilution, Millipore, Cat. # MAB377x), Alexa488-conjugated anti-IRF5 antibodies (1:200 dilution, R&D Systems, Cat. # IC4508G), and anti-SOX10 antibodies (R&D Systems, Cat. # AF2864) that were custom conjugated to Alexa647 (1:150 dilution, Cat# FCMAB317PE, Millipore) were used. DNA stain DAPI was used to label intact nuclei. From each sample and population, 100-150K nuclei were collected. We employed the native ChIP protocol (N-ChIP) in which chromatin fragmentation is performed using micrococcal nuclease (MNase) without crosslinking proteins to DNA (Sci Adv. 2018). We used anti-H3K27ac antibodies from Active Motif (Cat# 39133; rabbit polyclonal, 3 µg per sample). ChIP-Seq libraries were prepared with the NEBNext Ultra II DNA Library Prep Kit for Illumina (New England Biolabs, Cat. # E7645). The resulting libraries were sequenced on a NovaSeq 6000 instrument (Illumina), using paired-end 100 cycles protocol, to an average of 60 million read pairs per sample. For each diagnostic group, three input control samples obtained from MNAse-digested DNA were prepared and sequenced.