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Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3
Open accessAbstract
Autism is a common neurodevelopmental disorder of complex genetic etiology. Rett syndrome, an X-linked dominant disorder caused by MECP2 mutations, and Angelman syndrome, an imprinted disorder caused by maternal 15q11-q13 or UBE3A deficiency, have phenotypic and genetic overlap with autism. MECP2 encodes methyl-CpG-binding protein 2 that acts as a transcriptional repressor for methylated gene constructs but is surprisingly not required for maintaining imprinted gene expression. Here, we test the hypothesis that MECP2 deficiency may affect the level of expression of UBE3A and neighboring autism candidate gene GABRB3 without necessarily affecting imprinted expression. Multiple quantitative methods were used including automated quantitation of immunofluorescence and in situ hybridization by laser scanning cytometry on tissue microarrays, immunoblot and TaqMan PCR. The results demonstrated significant defects in UBE3A/E6AP expression in two different Mecp2 deficient mouse strains and human Rett, Angelman and autism brains compared with controls. Although no difference was observed in the allelic expression of several imprinted transcripts in Mecp2-null brain, Ube3a sense expression was significantly reduced, consistent with the decrease in protein. A non-imprinted gene from 15q11-q13, GABRB3, encoding the beta3 subunit of the GABAA receptor, also showed significantly reduced expression in multiple Rett, Angelman and autism brain samples, and Mecp2 deficient mice by quantitative immunoblot. These results suggest an overlapping pathway of gene dysregulation within 15q11-q13 in Rett, Angelman and autism and implicate MeCP2 in the regulation of UBE3A and GABRB3 expressions in the postnatal mammalian brain.
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Cites
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2
Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., & Zoghbi, H. Y. (1999) · Nature Genetics · doi:10.1038/13810 · Cited by 4,990
DNA Methylation-Related Chromatin Remodeling in Activity-Dependent Bdnf Gene Regulation
Martinowich, K., Hattori, D., Wu, H., Fouse, S., He, F., Hu, Y., Fan, G., & Sun, Y. E. (2003) · Science · doi:10.1126/science.1090842 · Cited by 1,405
Lewis, J. D., Meehan, R. R., Henzel, W. J., Maurer-Fogy, I., Jeppesen, P., Klein, F., & Bird, A. (1992) · Cell · doi:10.1016/0092-8674(92)90610-o · Cited by 1,371
Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice
Chen, R. Z., Akbarian, S., Tudor, M., & Jaenisch, R. (2001) · Nature Genetics · doi:10.1038/85906 · Cited by 1,275
Derepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2
Chen, W. G., Chang, Q., Lin, Y., Meissner, A., West, A. E., Griffith, E. C., Jaenisch, R., & Greenberg, M. E. (2003) · Science · doi:10.1126/science.1086446 · Cited by 1,232
Postnatal neurodevelopmental disorders: meeting at the synapse?
Zoghbi, H. Y. (2003) · Science · doi:10.1126/science.1089071 · Cited by 691
Murrell, A., Heeson, S., & Reik, W. (2004) · Nature Genetics · doi:10.1038/ng1402 · Cited by 556 · cited 1×
“Perhaps chromatin loop formation such has been recently demonstrated in the imprinted Igf2/ H19 region (57) is adversely affected by Mecp2 deficiency, as MeCP2 has been previously described to have matrix binding activity (58).”
BackgroundA Genomewide Screen for Autism: Strong Evidence for Linkage to Chromosomes 2q, 7q, and 16p
(2001) · The American Journal of Human Genetics · doi:10.1086/323264 · Cited by 453
Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers
Cook, E. H., Courchesne, R. Y., Cox, N. J., Lord, C., Gonen, D., Guter, S. J., Lincoln, A., Nix, K., Haas, R., Leventhal, B. L., et al. (1998) · The American Journal of Human Genetics · doi:10.1086/301832 · Cited by 369
Blatt, G. J., Fitzgerald, C. M., Guptill, J. T., Booker, A. B., Kemper, T. L., & Bauman, M. L. (2001) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1013238809666 · Cited by 322
Cited by
Genomic DNA methylation: the mark and its mediators.
Klose, R. J., & Bird, A. P. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.12.008 · Cited by 2,501
Advances in autism genetics: on the threshold of a new neurobiology
Abrahams, B. S., & Geschwind, D. H. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2346 · Cited by 1,866
Marchetto, M. C. N., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y., Chen, G., Gage, F. H., & Muotri, A. R. (2010) · Cell · doi:10.1016/j.cell.2010.10.016 · Cited by 1,329
The Story of Rett Syndrome: From Clinic to Neurobiology
Chahrour, M., & Zoghbi, H. Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.001 · Cited by 1,265
Searching for ways out of the autism maze: genetic, epigenetic and environmental clues
Persico, A. M., & Bourgeron, T. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.05.010 · Cited by 575
Autism spectrum disorders-a genetics review
Miles, J. H. (2011) · Genetics in Medicine · doi:10.1097/gim.0b013e3181ff67ba · Cited by 567
Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis
Baranzini, S. E., Wang, J., Gibson, R. A., Galwey, N., Naegelin, Y., Barkhof, F., Radue, E.-W., Lindberg, R. L. P., Uitdehaag, B. M. G., Johnson, M. R., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddn388 · Cited by 476
GABAA Receptor Downregulation in Brains of Subjects with Autism
Fatemi, S. H., Reutiman, T. J., Folsom, T. D., & Thuras, P. D. (2009) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-008-0646-7 · Cited by 439
GABAergic Interneurons Shape the Functional Maturation of the Cortex
Le Magueresse, C., & Monyer, H. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.011 · Cited by 425
Orefice, L. L., Zimmerman, A. L., Chirila, A. M., Sleboda, S. J., Head, J. P., & Ginty, D. D. (2016) · Cell · doi:10.1016/j.cell.2016.05.033 · Cited by 383
Nagarajan, R., Hogart, A., Gwye, Y., Martin, M. R., & LaSalle, J. M. (2006) · Epigenetics · doi:10.4161/epi.1.4.3514 · Cited by 347
Epigenetics of autism spectrum disorders
Schanen, N. C. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl213 · Cited by 341
Altered neural connectivity in excitatory and inhibitory cortical circuits in autism
Zikopoulos, B., & Barbas, H. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00609 · Cited by 313
How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis
Deth, R., Muratore, C., Benzecry, J., Power-Charnitsky, V.-A., & Waly, M. (2008) · NeuroToxicology · doi:10.1016/j.neuro.2007.09.010 · Cited by 325
Mechanisms of imprinting of the Prader-Willi/Angelman region
Horsthemke, B., & Wagstaff, J. (2008) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32364 · Cited by 320
Autism: A “Critical Period” Disorder?
LeBlanc, J. J., & Fagiolini, M. (2011) · Neural Plasticity · doi:10.1155/2011/921680 · Cited by 301
Molecular genetics of Rett syndrome: when DNA methylation goes unrecognized
Bienvenu, T., & Chelly, J. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1878 · Cited by 289
Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2
Giacometti, E., Luikenhuis, S., Beard, C., & Jaenisch, R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610593104 · Cited by 271
Melnyk, S., Fuchs, G. J., Schulz, E., Lopez, M., Kahler, S. G., Fussell, J. J., Bellando, J., Pavliv, O., Rose, S., Seidel, L., et al. (2012) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-011-1260-7 · Cited by 250
Neurobiological bases of autism–epilepsy comorbidity: a focus on excitation/inhibition imbalance
Bozzi, Y., Provenzano, G., & Casarosa, S. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.13595 · Cited by 250
Harada, M., Taki, M. M., Nose, A., Kubo, H., Mori, K., Nishitani, H., & Matsuda, T. (2011) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-1065-0 · Cited by 231
Autism Spectrum Disorders and Epigenetics
Grafodatskaya, D., Chung, B., Szatmari, P., & Weksberg, R. (2010) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2010.05.005 · Cited by 235
An epigenetic framework for neurodevelopmental disorders: From pathogenesis to potential therapy
Millan, M. J. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.11.015 · Cited by 229
Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome
Kriaucionis, S., Paterson, A., Curtis, J., Guy, J., MacLeod, N., & Bird, A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01665-05 · Cited by 219
Kim, K. C., Kim, P., Go, H. S., Choi, C. S., Park, J. H., Kim, H. J., Jeon, S. J., dela Pena, I. C., Han, S., Cheong, J. H., et al. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12147 · Cited by 212
Hogart, A., Leung, K. N., Wang, N. J., Wu, D. J., Driscoll, J., Vallero, R. O., Schanen, N. C., & LaSalle, J. M. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.061580 · Cited by 199
Self-citationFatemi, S. H., Reutiman, T. J., Folsom, T. D., Rooney, R. J., Patel, D. H., & Thuras, P. D. (2010) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-009-0924-z · Cited by 182
Tipping the balance of autism risk: potential mechanisms linking pesticides and autism
Shelton, J. F., Hertz-Picciotto, I., & Pessah, I. N. (2012) · Environmental Health Perspectives · doi:10.1289/ehp.1104553 · Cited by 164
Pluripotent stem cells in neurodegenerative and neurodevelopmental diseases
Marchetto, M. C. N., Winner, B., & Gage, F. H. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq159 · Cited by 152
Rett Syndrome: Exploring the Autism Link
Percy, A. K. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.149 · Cited by 144
Fatemi, S. H., Folsom, T. D., Kneeland, R. E., & Liesch, S. B. (2011) · The Anatomical Record · doi:10.1002/ar.21299 · Cited by 137
Trujillo, C. A., Adams, J. W., Negraes, P. D., Carromeu, C., Tejwani, L., Acab, A., Tsuda, B., Thomas, C. A., Sodhi, N., Fichter, K. M., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202012523 · Cited by 101
Mecp2 organizes juvenile social behavior in a sex-specific manner
Kurian, J. R., Bychowski, M. E., Forbes-Lorman, R. M., Auger, C. J., & Auger, A. P. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1345-08.2008 · Cited by 100
Evolving Role of MeCP2 in Rett syndrome and Autism
LaSalle, J. M., & Yasui, D. H. (2009) · Epigenomics · doi:10.2217/epi.09.13 · Cited by 98
Self-citationEpigenetic impacts of endocrine disruptors in the brain
Walker, D. M., & Gore, A. C. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.09.002 · Cited by 94
Jin, L.-W., Horiuchi, M., Wulff, H., Liu, X.-B., Cortopassi, G. A., Erickson, J. D., & Maezawa, I. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2778-14.2015 · Cited by 88
“…gene mutation (Amir et al., 1999; Levitt and Campbell, 2009) and MeCP2 regulation is also abnormal in a large subgroup of autistic individuals (Samaco et al., 2005; Moretti and Zoghbi, 2006; Nagarajan et al., 2008; Levitt and Campbell, 2009; Ramocki et al., 2009), our studies may implicate a…”
ResultFatemi, S. H., & Folsom, T. D. (2011) · Molecular Autism · doi:10.1186/2040-2392-2-6 · Cited by 84
Baron, C. A., Tepper, C. G., Liu, S. Y., Davis, R. R., Wang, N. J., Schanen, N. C., & Gregg, J. P. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl004 · Cited by 80
Ziats, M. N., & Rennert, O. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024691 · Cited by 75
Shepherd, G. M., & Katz, D. M. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.06.006 · Cited by 75
DNA methylation regulates tissue‐specific expression of Shank3
Beri, S., Tonna, N., Menozzi, G., Bonaglia, M. C., Sala, C., & Giorda, R. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04539.x · Cited by 74
Hernan, A. E., Alexander, A., Jenks, K. R., Barry, J., Lenck-Santini, P.-P., Isaeva, E., Holmes, G. L., & Scott, R. C. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.11.012 · Cited by 73
“Often these children not only have ictal EEG events, but also frequent interictal abnormalities.”
InfluentialGenetic modifiers of MeCP2 function in Drosophila
Cukier, H. N., Perez, A. M., Collins, A. L., Zhou, Z., Zoghbi, H. Y., & Botas, J. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000179 · Cited by 73
Enhanced Hypoxia Susceptibility in Hippocampal Slices From a Mouse Model of Rett Syndrome
Fischer, M., Reuter, J., Gerich, F. J., Hildebrandt, B., Hägele, S., Katschinski, D., & Müller, M. (2009) · Journal of Neurophysiology · doi:10.1152/jn.91124.2008 · Cited by 65
Immunologic and neurodevelopmental susceptibilities of autism
Pessah, I. N., Seegal, R. F., Lein, P. J., LaSalle, J., Yee, B. K., Van De Water, J., & Berman, R. F. (2008) · NeuroToxicology · doi:10.1016/j.neuro.2008.02.006 · Cited by 51
Self-citationBabij, R., Ferrer, C., Donatelle, A., Wacks, S., Buch, A. M., Niemeyer, J. E., Ma, H., Duan, Z. R. S., Fetcho, R. N., Che, A., et al. (2023) · Neuron · doi:10.1016/j.neuron.2022.10.037 · Cited by 35
García-Cabezas, M. Á., Barbas, H., & Zikopoulos, B. (2018) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2018.00070 · Cited by 30
(2013) · PubMed · Cited by 22
A Pooled Genome-Wide Association Study of Asperger Syndrome
Warrier, V., Chakrabarti, B., Murphy, L., Chan, A., Craig, I., Mallya, U., Lakatošová, S., Rehnstrom, K., Peltonen, L., Wheelwright, S., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0131202 · Cited by 11
Metadata
- Authors
- Samaco, R. C., Hogart, A., & LaSalle, J. M.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-12-22
- Volume
- 14
- Issue
- 4
- Pages
- 483-492
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2098914660
- Cited by
- 421
- References
- 12
- FWCI
- 13.64
- Type
- journal article
- Language
- en
- Open access
- green
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