Dual Requirement of CHD8 for Chromatin Landscape Establishment and Histone Methyltransferase Recruitment to Promote CNS Myelination and Repair
Open accessAbstract
Disruptive mutations in chromatin remodeler CHD8 cause autism spectrum disorders, exhibiting widespread white matter abnormalities; however, the underlying mechanisms remain elusive. We show that cell-type specific Chd8 deletion in oligodendrocyte progenitors, but not in neurons, results in myelination defects, revealing a cell-intrinsic dependence on CHD8 for oligodendrocyte lineage development, myelination and post-injury remyelination. CHD8 activates expression of BRG1-associated SWI/SNF complexes that in turn activate CHD7, thus initiating a successive chromatin remodeling cascade that orchestrates oligodendrocyte lineage progression. Genomic occupancy analyses reveal that CHD8 establishes an accessible chromatin landscape, and recruits MLL/KMT2 histone methyltransferase complexes distinctively around proximal promoters to promote oligodendrocyte differentiation. Inhibition of histone demethylase activity partially rescues myelination defects of CHD8-deficient mutants. Our data indicate that CHD8 exhibits a dual function through inducing a cascade of chromatin reprogramming and recruiting H3K4 histone methyltransferases to establish oligodendrocyte identity, suggesting potential strategies of therapeutic intervention for CHD8-associated white matter defects.
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The results showed that Chd8 modulates gene modules for oligodendrocyte differentiation and maturation, consistent with prior ChIP-Seq findings that CHD8 interacts directly with OPC maturation genes at perinatal stages.
“Our results showed that Chd8 modulates gene modules for oligodendrocyte differentiation and maturation, consistent with previously reported ChIP-Seq results showing that CHD8 interacts directly with OPC maturation genes at perinatal stages of development (28, 43).”
From In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes (2020) · cites this paper as [43]
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“Our results showed that Chd8 modulates gene programs for oligodendrocyte differentiation and maturation, consistent with previously reported ChIP-Seq results showing that CHD8 interacts directly with OPC maturation genes in the neonatal stage (Marie et al., 2018; Zhao et al., 2018).”
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“Made accessible by the chromatin remodeler CHD8, BRG1 forms chromatin remodeling complexes that activate CHD7, inducing a cascade of chromatin remodeling and gene transcription that inhibits nonoligodendroglial fates (Liu et al. 2007; Zhao et al. 2018).”
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MethodResultSelf-citationMyelTracer: A Semi-Automated Software for Myelin g -Ratio Quantification
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“During these early phases, Olig2 appears to cooperate downstream of the Chd8 chromatin remodeler with the Brg1-containing BAF complex to induce chromatin remodeling events that are essential for oligodendroglial development (Marie et al., 2018; Yu et al., 2013; Zhao et al., 2018).”
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“In addition, GO analysis revealed CHD8 influences neurogenesis, gliogenesis, Wnt signaling, and apoptosis [45].”
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“OPC differentiation medium contained the same components above except that 40 ng/ml triiodo-thyronine (Sigma Cat# T2877) without human basic fibro-blast growth factor and platelet-derived growth factor-aa as previously described (Zhao et al., 2018).”
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“Many other interactions between COMPASS and other chromatinopathy proteins have been uncovered, such as with the chromatin remodeler CHD8, which activates expression of BRG1-associated BAF complexes and recruits MLL/KMT2 COMPASS complexes to promote central nervous system myelination and myelin repair (18,40,41).”
BackgroundSentinels of chromatin: chromodomain helicase DNA-binding proteins in development and diseasePreprint
Alendar, A., & Berns, A. J. M. (2021) · Genes & Development · doi:10.1101/gad.348897.121 · Cited by 65 · see citing works
“Moreover, CHD enzymes are also critical for the maturation of glial cells andmyelination of the central nervous system (CNS; CHD7/8) (Feng et al. 2013; He et al. 2016; Doi et al. 2017; Marie et al. 2018; Zhao et al. 2018a) and peripheral nervous system (CHD4) (Fig.”
BackgroundRegulation of neuronal connectivity in the mammalian brain by chromatin remodeling
Goodman, J. V., & Bonni, A. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.04.010 · Cited by 60 · see citing works
“Notably, MRI of the brain in CHARGE syndrome patients and autism patients carrying a null Chd8 allele reveals reduction in white matter volume [65,70].”
BackgroundResultInfluentialEEF1A1 deacetylation enables transcriptional activation of remyelination
Duman, M., Vaquie, A. M., Nocera, G., Heller, M., Stumpe, M., Sankar, D. S., Dengjel, J., Meijer, D., Yamaguchi, T., Matthias, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17243-z · Cited by 56 · see citing works
Oligodendrocyte dysfunction due to Chd8 mutation gives rise to behavioral deficits in mice
Kawamura, A., Katayama, Y., Nishiyama, M., Shoji, H., Tokuoka, K., Ueta, Y., Miyata, M., Isa, T., Miyakawa, T., Hayashi‐Takagi, A., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa036 · Cited by 56 · see citing works
Berry, K., Wang, J., & Lu, Q. R. (2020) · F1000Research · doi:10.12688/f1000research.20904.1 · Cited by 50 · see citing works
“…to promotor elements near transcription start sites marked by an activating histone mark H3K4me3 in OPCs and oligodendrocytes where it recruits an H3K4 activating histone methyltransferase MLL2 (mixed lineage leukemia 2) complex to drive expression of oligodendrocyte lineage genes 41 .”
BackgroundInfluentialSelf-citationSmall molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration
Jiang, D., Li, T., Guo, C., Tang, T.-S., & Liu, H. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-00953-4 · Cited by 54 · see citing works
The autism-associated protein CHD8 is required for cerebellar development and motor function
Kawamura, A., Katayama, Y., Kakegawa, W., Ino, D., Nishiyama, M., Yuzaki, M., & Nakayama, K. I. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108932 · Cited by 50 · see citing works
Resolving the Synaptic versus Developmental Dichotomy of Autism Risk Genes
Heavner, W. E., & Smith, S. E. P. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.01.009 · Cited by 48 · see citing works
Qki activates Srebp2-mediated cholesterol biosynthesis for maintenance of eye lens transparency
Shin, S., Zhou, H., He, C., Wei, Y., Wang, Y., Shingu, T., Zeng, A., Wang, S., Zhou, X., Li, H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22782-0 · Cited by 48 · see citing works
Coll-Tané, M., Gong, N. N., Belfer, S. J., van Renssen, L. V., Kurtz‐Nelson, E. C., Szuperák, M., Eidhof, I., van Reijmersdal, B., Terwindt, I., Durkin, J., et al. (2021) · Science Advances · doi:10.1126/sciadv.abe2626 · Cited by 47 · see citing works
Bohlen, J. F., Cleary, C. M., Das, D., Sripathy, S. R., Sadowski, N., Shim, G., Kenney, R. F., Buchler, I. P., Banerji, T., Scanlan, T. S., et al. (2023) · Brain · doi:10.1093/brain/awad057 · Cited by 43 · see citing works
Wang, J., Yang, L., Dong, C., Wang, J., Xu, L., Qiu, Y., Weng, Q., Zhao, C., Xin, M., & Lu, Q. R. (2020) · Science Advances · doi:10.1126/sciadv.aaz6477 · Cited by 42 · see citing works
“In situ hybridization was performed as described previously (16).”
BackgroundMethodInfluentialSelf-citationCHD8 dosage regulates transcription in pluripotency and early murine neural differentiation
Sood, S., Weber, C. M., Hodges, H. C., Krokhotin, A., Shalizi, A., & Crabtree, G. R. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1921963117 · Cited by 42 · see citing works
“In human ASD patients with disruptive mutations in CHD8, corpus callosum hypogenesis is a prevalent phenotype (28).”
BackgroundWade, A. A., Lim, K. J., Catta-Preta, R., & Nord, A. S. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00481 · Cited by 38 · see citing works
“Finally, we included 1 cell-type-specific ChIP-seq study profiling oligodendrocyte precursors and mature oligodendroctyes isolated from rat brain (Zhao et al., 2018).”
MethodLong non-coding RNAs: the tentacles of chromatin remodeler complexes
NEVE, B. P., Jonckheere, N., Vincent, A., & SEUNINGEN, I. V. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03646-0 · Cited by 41 · see citing works
Chromatin Remodeler CHD8 in Autism and Brain Development
Hoffmann, A., & Spengler, D. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10020366 · Cited by 41 · see citing works
“[41] strongly support a role of Chd8 in chromatin remodeling during OL lineage‐specific gene expression.”
BackgroundResultInfluentialElsesser, O., Fröb, F., Küspert, M., Tamm, E. R., Fujii, T., Fukunaga, R., & Wegner, M. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz376 · Cited by 38 · see citing works
“Further considering that the known chromatin remodeling activities appear to be active in the same pathway and act in a cascade-like fashion with Chd8containing remodelers involved in Brg1 induction and the Brg1-containing BAF complex involved in Chd7 induction (8,11), it is reasonable to assume that major chromatin r…”
BackgroundExcitatory neuronal CHD8 in the regulation of neocortical development and sensory-motor behaviors
Kweon, H., Jung, W. B., Im, G. H., Ryoo, J., Lee, J.-H., Do, H., Choi, Y., Song, Y.-H., Jung, H., Park, H., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108780 · Cited by 36 · see citing works
Identifying oligodendrocyte enhancers governing Plp1 expression
Kim, D., An, H., Fan, C., & Park, Y. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab184 · Cited by 35 · see citing works
Regulators of Oligodendrocyte DifferentiationPreprint
Emery, B., & Wood, T. L. (2024) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041358 · Cited by 35 · see citing works
Samudyata, S., Castelo‐Branco, G., & Liu, J. (2020) · Glia · doi:10.1002/glia.23820 · Cited by 31 · see citing works
“…remodeling protein CHD8 plays a critical role in establishing an accessible chromatin landscape and recruits ASH2L and WDR5, two components in the MLL/KMT2 KMT complex, to deposit H3K4me3 around the proximal promoter regions to establish OL identity (He et al., 2016; C. Zhao et al., 2018).”
BackgroundQki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis
Zhou, X., Shin, S., He, C., Zhang, Q., Rasband, M. N., Ren, J., Dai, C., Zorrilla-Veloz, R. I., Shingu, T., Yuan, L., et al. (2021) · eLife · doi:10.7554/elife.60467 · Cited by 33 · see citing works
Pan, L., Trimarco, A., Zhang, A. J., Fujimori, K., Urade, Y., Sun, L. O., Taveggia, C., & Zhang, Y. (2023) · eLife · doi:10.7554/elife.77441 · Cited by 31 · see citing works
Adenosine Actions on Oligodendroglia and Myelination in Autism Spectrum Disorder
Shen, H., Huang, N., Reemmer, J., & Xiao, L. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00482 · Cited by 30 · see citing works
“Moreover, chromatin-remodeling protein CHD8, an ASD susceptibility gene, has also been found to play a vital role in oligodendroglial development and remyelination (Zhao et al., 2018).”
BackgroundExperimental Models to Study Autism Spectrum Disorders: hiPSCs, Rodents and Zebrafish
Pensado‐López, A., Veiga-Rúa, S., Carracedo, Á., Allegue, C., & Sanchez, L. E. (2020) · Genes · doi:10.3390/genes11111376 · Cited by 31 · see citing works
CHD8 mutations increase gliogenesis to enlarge brain size in the nonhuman primate
Li, B., Zhao, H., Tu, Z., Yang, W., Han, R., Wang, L., Luo, X., Pan, M., Chen, X., Zhang, J., et al. (2023) · Cell Discovery · doi:10.1038/s41421-023-00525-3 · Cited by 30 · see citing works
Autism-associated miR-873 regulates ARID1B, SHANK3 and NRXN2 involved in neurodevelopment
Lü, J., Zhu, Y., Williams, S., Watts, M. E., Tonta, M. A., Coleman, H. A., Parkington, H. C., & Claudianos, C. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-01106-8 · Cited by 29 · see citing works
Doi, H., Matsuda, T., Sakai, A., Matsubara, S., Hoka, S., Yamaura, K., & Nakashima, K. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2107596118 · Cited by 29 · see citing works
“6E), chromatin remodeling factors that augment chromatin accessibility (36, 37).”
Chromatin remodelers in oligodendroglia
Parras, C. M., Marie, C., Zhao, C., & Lu, Q. R. (2020) · Glia · doi:10.1002/glia.23837 · Cited by 28 · see citing works
“Interestingly, Chd8, the Chd7 paralogue, presents a similar expression pattern to Chd7 in oligodendroglia, with Chd8 protein present in OPCs, having its highest levels in iOLs, and decreasing to almost undetectable levels in mOLs (Marie et al., 2018; Zhao et al., 2018), in agreement with Chd8 transcripts in postnatal…”
BackgroundMethodResultInfluentialSelf-citationTu, Z., Wang, C., Davis, A. K., Hu, M., Zhao, C., Xin, M., Lu, Q. R., & Zheng, Y. (2021) · Blood · doi:10.1182/blood.2020009997 · Cited by 32 · see citing works
Self-citationDHHC5 facilitates oligodendrocyte development by palmitoylating and activating STAT3
Ma, Y., Liu, H., Ou, Z., Chen, Q., Xing, R., Wang, S., Han, Y., Zhao, T., & Chen, Y. (2021) · Glia · doi:10.1002/glia.24113 · Cited by 27 · see citing works
“Intrinsically, myelination is controlled by transcription factors, post-translational regulators and chromatin remodeling process (He et al., 2016, 2018; Marie et al., 2018; Wang et al., 2017; Zhao et al., 2018).”
BackgroundCHD8 suppression impacts on histone H3 lysine 36 trimethylation and alters RNA alternative splicing
Kerschbamer, E., Arnoldi, M., Tripathi, T., Pellegrini, M., Maturi, S., Erdin, S., Salviato, E., Leva, F. D., Sebestyén, E., Dassi, E., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac1134 · Cited by 27 · see citing works
Dermitzakis, I., Manthou, M., Meditskou, S., Miliaras, D., Kesidou, E., Boziki, M., Petratos, S., Grigoriadis, N., & Theotokis, P. (2022) · Current Issues in Molecular Biology · doi:10.3390/cimb44070222 · Cited by 26 · see citing works
“22 NK2 homeobox 2 Specification; Proliferation; Differentiation [37,108,123,124, 268] NKX2-6 8p21.”
BackgroundInfluentialMegagiannis, P., Yuan, M., Yan, R., Yuan, L., Wilde, J. J., Eckersberg, H., Suresh, R., Tan, X., Chen, H., Farmer, W. T., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114637 · Cited by 26 · see citing works
“41 This analytic pipeline was applied to all serial sections, and comparisons were made between control and global cKO groups (Figures S4A–S4F).”
Sun, Y., Chen, X., Ou, Z., Wang, Y., Chen, W., Zhao, T., Liu, C., & Chen, Y. (2021) · Advanced Science · doi:10.1002/advs.202103065 · Cited by 24 · see citing works
Boshans, L. L., Factor, D., Singh, V., Liu, J., Zhao, C.-T., Măndoiu, I., Lu, Q. R., Casaccia, P., Tesar, P., & Nishiyama, A. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00829 · Cited by 15 · see citing works
“Furthermore, Chd8 functions upstream of Brg1 and initiates a cascade of nucleosome remodeling events mediated by Brg1 and Chd7 (Zhao et al., 2018).”
BackgroundSelf-citationMaternal-infant probiotic transmission mitigates early-life stress-induced autism in mice
Qing, L., Qian, X., Zhu, H., Wang, J., Sun, J., Jin, Z., Tang, X., Zhao, Y., Wang, G., Zhao, J., et al. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2456584 · Cited by 26 · see citing works
Verma, R., Chen, X., Xin, D. E., Luo, Z., Ogurek, S., Xin, M., Rao, R., Berry, K., & Lu, Q. R. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-1577 · Cited by 23 · see citing works
Self-citationA New Acquaintance of Oligodendrocyte Precursor Cells in the Central Nervous System
Ma, Z., Zhang, W., Wang, C., Su, Y., Yi, C., & Niu, J. (2024) · Neuroscience Bulletin · doi:10.1007/s12264-024-01261-8 · Cited by 24 · see citing works
Self-citationThe NuRD complex in neurodevelopment and disease: a case of sliding doors
Boulasiki, P., Tan, X. W., Spinelli, M., & Riccio, A. (2023) · Cells · doi:10.3390/cells12081179 · Cited by 22 · see citing works
“Interestingly, autistic patients carrying a defective CHD8 gene have shown decreased white matter density and defects of myelination [74].”
BackgroundMosaic integration of spatial multi-omics with SpaMosaic
Yan, X., Ang, K. S., Ang, K. S., van Olst, L., Edwards, A., Watson, T., Zheng, R., Zhang, D., Fan, R., Li, M., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02573-3 · Cited by 23 · see citing works
Dong, C., Zhao, C., Chen, X. '., Berry, K., Wang, J., Zhang, F., Liao, Y., Han, R., Ogurek, S., Xu, L., et al. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.2400-21.2022 · Cited by 21 · see citing works
Self-citationLi, Y.-J., Li, C., Li, C., Hu, D., Xv, Z.-B., Zhang, S., Li, Q., Zhang, P., Tian, B., Lan, X., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03167-w · Cited by 20 · see citing works
“According to the reference [39], genomic occupancy analyses reveal that CHD8 establishes an accessible chromatin landscape, and recruits MLL/KMT2 histone methyltransferase complexes distinctively around proximal promoters to promote oligodendrocyte differentiation.”
BackgroundThe Role of Oligodendrocytes in Neurodegenerative Diseases: Unwrapping the Layers
Panichi, L. B., Stanca, S., Dolciotti, C., & Bongioanni, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104623 · Cited by 20 · see citing works
“Technologies such as CRISPR/Cas9 offer the potential to correct specific ge-netic mutations underlying myelin disorders [144], while modulation of DNA methylation and histone acetylation pathways has been shown to influence OPC differentiation and re-myelination capacity [145,146].”
Single-Cell Transcriptomics Supports a Role of CHD8 in Autism
Hoffmann, A., & Spengler, D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063261 · Cited by 19 · see citing works
“In utero, editing of Chd8 turned out to disrupt oligodendrocyte gene expression modules reminiscent of findings from heterozygote Chd8 mice [60,61].”
BackgroundResultJiménez, J. A., Simon, J. M., Hu, W., Moy, S. S., Harper, K. M., Liu, C., Lü, K., & Zylka, M. J. (2022) · Scientific Reports · doi:10.1038/s41598-022-09533-x · Cited by 19 · see citing works
The epigenetic landscape of oligodendrocyte lineage cells
Selcen, I., Prentice, E., & Casaccia, P. (2023) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14959 · Cited by 20 · see citing works
Kawamura, A., & Nishiyama, M. (2023) · Communications Biology · doi:10.1038/s42003-023-04968-y · Cited by 19 · see citing works
“Consistent with previous fi ndings that CHD8 promotes the adoption of open chromatin structures in several cell types 19,20,33 , we found that Chd8 ablation in the adult brain reduced chromatin accessibility at the loci of activity-dependent genes.”
A Novel Chd8 Mutant Mouse Displays Altered Ultrasonic Vocalizations and Enhanced Motor Coordination
Hulbert, S. W., Wang, X., Gbadegesin, S. O., Xu, Q., Xu, X., & Jiang, Y. (2020) · Autism Research · doi:10.1002/aur.2353 · Cited by 18 · see citing works
“, 2016], myelination defects [Zhao et al., 2018], increased proliferation of neuronal progenitors [Gompers et al.”
BackgroundInfluentialLi, T., Guo, M., Xie, P., Liu, S., & Luan, G. (2022) · Current Neuropharmacology · doi:10.2174/1570159x20666220706100136 · Cited by 19 · see citing works
“Besides, ASD and its comorbidities are associated with hypomyelin and oligodendrocyte dysfunction [114].”
Haddad, B., Dankó, T., Chanda, S., Batista, P. J., Litzenburger, U. M., Lee, Q. Y., Ng, Y. H., Sebin, A., Chang, H. Y., Südhof, T. C., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-23614-x · Cited by 18 · see citing works
Chromatin remodeler CHD8 is required for spermatogonial proliferation and early meiotic progression
Nitahara, K., Kawamura, A., Kitamura, Y., Kato, K., Namekawa, S. H., & Nishiyama, M. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad1256 · Cited by 18 · see citing works
“Disorders caused by Chd8 mutation have a shared molecular etiology involving H3K4me3 histone methyltransferase activity, both in the testes (this study) and the nervous system ( 71 ).”
BackgroundEpigenetic regulation of myelination in health and disease
Lu, G., Zhang, M., Wang, J., Zhang, K., Wu, S., & Zhao, X. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14337 · Cited by 16 · see citing works
“Deletion of Chd8 in oligodendrocyte progenitors resulted in severe myelination deficits, revealing a cell‐intrinsic dependence on CHD8 for oligodendrocyte lineage development, myelination, and post‐injury remyelination (Zhao et al., 2018).”
BackgroundMicroglial ASD-related genes are involved in oligodendrocyte differentiation
Takanezawa, Y., Tanabe, S., Kato, D., Ozeki, R., Komoda, M., Suzuki, T., Baba, H., & Muramatsu, R. (2021) · Scientific Reports · doi:10.1038/s41598-021-97257-9 · Cited by 17 · see citing works
Chromatin modification and epigenetic control in functional nerve regeneration
Berry, K., & Lu, Q. R. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.07.009 · Cited by 16 · see citing works
Self-citationOligodendroglial Epigenetics, from Lineage Specification to Activity-Dependent Myelination
Pruvost, M., & Moyon, S. (2021) · Life · doi:10.3390/life11010062 · Cited by 17 · see citing works
“In particular, the ablation of Chd8 in neonatal OPCs results in massive hypomyelination of the CNS, leading to seizures and eventually death of the mice at postnatal day 21 [138].”
BackgroundInfluentialIdentifying an oligodendrocyte enhancer that regulatesOlig2expression
Fan, C., Kim, D., An, H., & Park, Y. (2022) · Human Molecular Genetics · doi:10.1093/hmg/ddac249 · Cited by 16 · see citing works
“gov/sra): GSE42454 (H3K9me3, Brg1, Olig2, H3K27ac, H3K4me3) (6), GSE72727 (Chd7, Sox10) (51), GSE119816 (Seh1) (52), GSE76411 (Hdac3, p300) (53), GSE82165 (Suz12) (54), GSE65119 (Tcf7l2) (55), GSE84011 (Olig2, H3K27ac) (56), GSE64703 (Sox10) (57), GSE107919 (Chd7, Chd8) (58), GSE101535 (Zfp24) (59) and GSE79243 (Klf6)…”
Neurodevelopmental functions of CHD8: new insights and questions
Basson, M. A. (2024) · Biochemical Society Transactions · doi:10.1042/bst20220926 · Cited by 17 · see citing works
Shi, X.-Y., He, Y., Ge, M.-Y., Liu, P., Zheng, P., & Li, Z. (2025) · Acta Pharmacologica Sinica · doi:10.1038/s41401-025-01492-z · Cited by 13 · see citing works
“According to the previous studies [40], the corpus callosum containing the lesions was dissected after transcardial perfusion and fi xed in 2.5% glutaraldehyde at 4 °C overnight.”
InfluentialChen, X. '., Chen, T., Dong, C., Chen, H., Dong, X., Yang, L., Hu, L., Wang, H., Wu, B., Yao, Y., et al. (2022) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2022.02.011 · Cited by 13 · see citing works
Self-citationThe stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina
Pruvost, M., Patzig, J., Yattah, C., Selcen, I., Hernandez, M., Park, H., Moyon, S., Liu, S., Morioka, M. S., Shopland, L. S., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112848 · Cited by 12 · see citing works
Alpsoy, A., Sood, S., & Dykhuizen, E. C. (2021) · Biology · doi:10.3390/biology10040272 · Cited by 12 · see citing works
“CHD8 is proposed to recruit methyltransferases that affect transcription [38,40]; however, it is not yet clear whether, or how, the ATPase function of CHD8 is involved.”
BackgroundSystemic and intrinsic functions of ATRX in glial cell fate and CNS myelination in male mice
Rowland, M. E., Jiang, Y., Shafiq, S., Ghahramani, A., Pena-Ortiz, M., Dumeaux, V., & Bérubé, N. G. (2023) · Nature Communications · doi:10.1038/s41467-023-42752-y · Cited by 12 · see citing works
“Chromatin occupancy of CHD8 in OPCs is greater than that of CHD7 66 , and CHD8 acts upstream of the Brg1-containing BAF complex and Olig2, both of which promote CHD7 expression 67 .”
BackgroundAbbas, E., Hassan, M. A., Sokpor, G., Kiszka, K. A., Pham, L., Kerimoglu, C., Fischer, A., Nguyen, H. P., Staiger, J. F., & Tuoc, T. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.619538 · Cited by 11 · see citing works
Merour, E., Hmidan, H., Marie, C., Helou, P.-H., Lu, H., Potel, A., Huré, J.-B., Clavairoly, A., Shih, Y. P., Goudarzi, S., et al. (2022) · eLife · doi:10.7554/elife.80273 · Cited by 11 · see citing works
Self-citationPijuan, I., Balducci, E., Soto‐Sánchez, C., Fernández, E., Barallobre, M. J., & Arbonés, M. L. (2022) · Scientific Reports · doi:10.1038/s41598-022-24284-5 · Cited by 11 · see citing works
Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors
Lee, S. Y., Kweon, H., Kang, H., & Kim, E. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1022306 · Cited by 10 · see citing works
Dysregulation of myelination‐related genes in schizophrenia
Bergstrom, J. J. D., & Fu, M. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16152 · Cited by 10 · see citing works
“Interestingly, mutations in another chromatin remodeling protein, CHD8, are associated with autism spectrum disorder, and OPC-specific deletion of Chd8 in mice is associated with impaired myelination (Zhao et al., 2018 ).”
Yim, K., Baumgartner, M., Krenzer, M., Larios, M. F. R., Hill-Terán, G., Nottoli, T., Muhle, R., & Noonan, J. P. (2025) · Cell Genomics · doi:10.1016/j.xgen.2025.100986 · Cited by 12 · see citing works
Mechanisms of brain overgrowth in autism spectrum disorder with macrocephaly
Currey, L., Harvey, T. J., Pelenyi, A., Piper, M., & Thor, S. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1586550 · Cited by 8 · see citing works
“…ASD – CHD8 – interacts with β -catenin, as well as other factors such as E2F, REST, and KMT2A, to regulate cell cycle, neuronal identity, and oligodendrocyte differentiation, respectively (Weissberg and Elliott, 2021; Subtil-Rodríguez et al., 2014; Katayama et al., 2016; Zhao et al., 2018).”
Adès, N., & Bouslama‐Oueghlani, L. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03490-x · Cited by 7 · see citing works
Genetic and epigenetic regulation of Treg cell fitness by autism-related chromatin remodeler CHD8
Yang, J., Wang, C., Nayak, R. C., Kolla, M., Cai, M., Pujato, M. A., Zheng, Y., Lu, Q. R., & Guo, F. (2025) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-025-00711-z · Cited by 8 · see citing works
“To investigate the role of CHD8 in Tregs, we crossed Chd8 Flox/Flox mice [21] with Foxp3 YFP − cre transgenic mice, which express a knocked-in YFP/iCre-recombinase fusion protein under the control of X chromosome-linked Foxp3 gene, to generate Treg-spe-cific Chd8 − / − mice (Chd8 Flox/Flox Foxp3…”
InfluentialSelf-citationTu, Z., Fan, C., Davis, A. K., Hu, M., Wang, C., Dandamudi, A., Seu, K. G., Kalfa, T. A., Lu, Q. R., & Zheng, Y. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111072 · Cited by 7 · see citing works
“Besides its well-known functions of restricting P53 and β-catenin signaling through histone H1 binding, CHD8 is also critical in transcription regulation in neural progenitors and oligodendrocytes (Durak et al., 2016; Nishiyama et al., 2009; Sood et al., 2020; Thompson et al., 2008; Zhao et al., 2018).”
InfluentialSelf-citationMacromolecular Complex Including MLL3, Carabin and Calcineurin Regulates Cardiac Remodeling
Pane, R., Laib, L., Formoso, K., Détrait, M., Sainte–Marie, Y., Bourgailh, F., Ruffenach, N., Faugeras, H., Simon, I., Lhuillier, É., et al. (2023) · Circulation Research · doi:10.1161/circresaha.123.323458 · Cited by 6 · see citing works
“34 In contrast to physiological conditions, MLL3 was largely localized at the promoters (32”
BackgroundWen, C., Xu, Z., Cao, F., Yuan, Q., Su, W., & Huang, Z. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111431 · Cited by 6 · see citing works
SLC44A1 deficiency impedes myelin development in the central nervous system
Chen, Q., Chen, X., Li, Z., Shao, Q., Huang, H., Zhou, W., Qiu, M. S., Su, Z., Liu, P., & He, C. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116617 · Cited by 7 · see citing works
Self-citationLong Noncoding RNAs in CNS Myelination and Disease
Zhang, J., Guan, M.-L., Zhou, X., Berry, K., He, X.-L., & Lu, Q. R. (2022) · The Neuroscientist · doi:10.1177/10738584221083919 · Cited by 6 · see citing works
Self-citationElucidating neuroepigenetic mechanisms to inform targeted therapeutics for brain disorders
Weekley, B. H., Ahmed, N. I., & Maze, I. S. (2025) · iScience · doi:10.1016/j.isci.2025.112092 · Cited by 7 · see citing works
“113,114 Importantly, based on these findings, potential treatment strategies can now be tested in these rodent model systems in future studies.”
Age-differential sexual dimorphisms in CHD8-S62X-mutant mouse synapses and transcriptomes
Lee, S. Y., Kweon, H., Kang, H., & Kim, E. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1111388 · Cited by 6 · see citing works
“Previous studies on Chd8-mutant mice and human neurons suggested multiple mechanisms that may underlie CHD8-related brain deficits (Sugathan et al., 2014; Cotney et al., 2015; Wang et al., 2015; Breuss and Gleeson, 2016; Durak et al., 2016; Katayama et al., 2016; Gompers et al., 2017; Platt et al., 2017; Wang et al.,…”
BackgroundWright, J. L., Jiang, Y., Nayar, S. G., Rajeeve, V., Cutillas, P. R., Li, H., & Richardson, W. D. (2025) · Glia · doi:10.1002/glia.70006 · Cited by 5 · see citing works
“…results from stage-specific interactions with chromatin remodeling complexes (CRCs), with which it cooperates to direct site-and stage-specific remodeling of nucleosomes along the genome (Yu et al. 2013; He et al. 2016; Marie et al. 2018; Zhao et al. 2018; Elsesser et al. 2019; Parras et al. 2020).”
InfluentialWeissberg, O., Harari, R., Dogun, C., Getselter, D., & Elliott, E. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03468-3 · Cited by 5 · see citing works
Chromatin remodeler Chd7 regulates reactive astrogliosis after ischemic stroke
Nagao, M., Maekawa, T., Yamazaki, A., & Ogata, T. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116590 · Cited by 5 · see citing works
Uncovering oligodendrocyte enhancers that control Cnp expression
Fan, C., An, H., Kim, D., & Park, Y. (2023) · Human Molecular Genetics · doi:10.1093/hmg/ddad141 · Cited by 5 · see citing works
“…Brg1, Olig2, H3K27ac, H3K4me3) [60], GSE72727 (Chd7, Sox10) [61], GSE119816 (Seh1) [62], GSE76411 (Hdac3, p300) [63], GSE82165 (Suz12) [64], GSE65119 (Tcf7l2) [65], GSE84011 (Olig2, H3K27ac) [66], GSE64703 (Sox10) [67], GSE107919 (Chd7, Chd8) [68], GSE101535 (Zfp24) [69], and GSE79243 (Klf6) [70].”
Duan, J., Zeng, D., Wu, T., Luo, Z., Jingwen, G., Tan, W., & Zeng, Y. (2025) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2025.102759 · Cited by 4 · see citing works
Development of Oligodendroglia and Myelin
Huang, H., Xu, X., & Qiu, M. S. (2025) · Advances in neurobiology · doi:10.1007/978-3-031-87919-7_3 · Cited by 4 · see citing works
- Authors
- Zhao, C., Dong, C., Frah, M., Deng, Y., Marie, C., Zhang, F., Xu, L., Ma, Z., Dong, X., Lin, Y., Koenig, S., Nait-Oumesmar, B., Martin, D. M., Wu, L. N., Xin, M., Zhou, W., Parras, C., & Lu, Q. R.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Centre National de la Recherche Scientifique (FR)
- Children's Hospital of Fudan University (CN)
- University of Michigan (US)
- Fudan University (CN)
- Corresponding author
- Zhao, Chuntao
- Zhou, Wenhao
- Lu, Q. Richard
- ORCID
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 45
- Issue
- 6
- Pages
- 753-768.e8
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC6063525
- OpenAlex
- W2808893326
- Cited by
- 146
- References
- 68
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 12 · 2023: 18 · 2022: 21 · 2021: 25 · 2020: 22 · 2019: 8 · 2018: 3
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- National Natural Science Foundation of China (NMSS RG-1501-02851, 81720108018)
- National Multiple Sclerosis Society (RG1508)
- National Institutes of Health (R01NS072427, R01NS075243)
- Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- CHD8, myelination, remyelination, chromatin remodeling, SWI/SNF complex, CHD7, H3K4 methylation, histone demethylase, chromatin accessibility, white matter abnormalities, autism spectrum disorder, CNS injury repair
- MeSH terms
- Histone Methyltransferases, Animals, Cell Differentiation, Chromatin, DNA Helicases, DNA-Binding Proteins, Myelin Sheath, Nerve Fibers, Myelinated, Nuclear Proteins, Oligodendroglia, Histone-Lysine N-Methyltransferase, Transcription Factors, Rats, Sprague-Dawley, Mice, Knockout, Chromatin Assembly and Disassembly, Mice, Rats
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