MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
Open accessAbstract
Mutations in the gene encoding the transcriptional repressor methyl-CpG binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome. Loss of function as well as increased dosage of the MECP2 gene cause a host of neuropsychiatric disorders. To explore the molecular mechanism(s) underlying these disorders, we examined gene expression patterns in the hypothalamus of mice that either lack or overexpress MeCP2. In both models, MeCP2 dysfunction induced changes in the expression levels of thousands of genes, but unexpectedly the majority of genes (∼85%) appeared to be activated by MeCP2. We selected six genes and confirmed that MeCP2 binds to their promoters. Furthermore, we showed that MeCP2 associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target. These studies suggest that MeCP2 regulates the expression of a wide range of genes in the hypothalamus and that it can function as both an activator and a repressor of transcription.
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Elimination of MeCP2 affects the expression of a profound number of pathways in the CNS, making it difficult to pinpoint which pathways play a key role in RTT pathology.
“While Mecp2 mutant mice are an excellent model for RTT, elimination of MeCP2 affects the expression of a profound number of pathways in the CNS, making it difficult to pinpoint which ones play a key role in pathology [77,89,90].”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [77]
The gene-expression results (section labeled Abstract; page not provided) report thousands of altered genes in the hypothalamus of Mecp2-null and overexpressing mice, across distinct functional categories. The concluding passage says that restoring each affected gene may be challenging, but it does not say that identifying the pathways key to RTT pathology is difficult. The study examined the hypothalamus, not the CNS as a whole. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMeCP2 may also facilitate transcriptional activation, chromatin compaction and mRNA splicing, while interacting with other regulatory proteins.
“However, MeCP2 may also facilitate transcriptional activation [77], chromatin compaction [78,79] and mRNA splicing [80,81], while also interacting with a host of other regulatory proteins involved in a variety of molecular pathways [81–84].”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [77]
MeCP2 may be defined as a transcriptional modulator.
“Altogether, multiple studies suggest that genes can be activated or repressed by MeCP2, depending upon the cellular context [77,89,90], suggesting that MeCP2 may be defined as a transcriptional modulator.”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [77]
MeCP2 binding to methylated DNA has a biphasic impact on transcription.
“These data are consistent with another study showing that MeCP2 binding to methylated DNA has a biphasic impact on transcription.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [123]
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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 · see citing works
Self-citationNan, X., Ng, H.-H., Johnson, C. A., Laherty, C. D., Turner, B. M., Eisenman, R. N., & Bird, A. (1998) · Nature · doi:10.1038/30764 · Cited by 3,440 · see citing works
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
Jones, P. L., Veenstra, G. J. C., Wade, P. A., Vermaak, D., Kass, S. U., Landsberger, N., Strouboulis, J., & Wolffe, A. P. (1998) · Nature Genetics · doi:10.1038/561 · Cited by 2,734 · see citing works
A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome
Guy, J., Hendrich, B., Holmes, M., Martin, J. E., & Bird, A. (2001) · Nature Genetics · doi:10.1038/85899 · Cited by 1,558 · see citing works
DNA Methylation-Related Chromatin Remodeling in Activity-Dependent <i>Bdnf</i> 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 · see citing works
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 · see citing works
Zhou, Z., Hong, E. J., Cohen, S., Zhao, W.-N., Ho, H.-Y. H., Schmidt, L., Chen, W. G., Lin, Y., Savner, E., Griffith, E. C., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.037 · Cited by 877 · see citing works
Mild overexpression of MeCP2 causes a progressive neurological disorder in mice
Collins, A. L., Levenson, J. M., Vilaythong, A. P., Richman, R., Armstrong, D. L., Noebels, J. L., David Sweatt, J., & Zoghbi, H. Y. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh282 · Cited by 626 · see citing works
Self-citationThe disease progression of Mecp2 mutant mice is affected by the level of BDNF expression
Chang, Q., Khare, G., Dani, V., Nelson, S., & Jaenisch, R. (2006) · Neuron · doi:10.1016/j.neuron.2005.12.027 · Cited by 578 · see citing works
MeCP2 Controls Excitatory Synaptic Strength by Regulating Glutamatergic Synapse Number
Chao, H.-T., Zoghbi, H. Y., & Rosenmund, C. (2007) · Neuron · doi:10.1016/j.neuron.2007.08.018 · Cited by 511 · see citing works
Self-citationHomeostatic regulation of MeCP2 expression by a CREB-induced microRNA
Klein, M. E., Lioy, D. T., Ma, L., Impey, S., Mandel, G., & Goodman, R. H. (2007) · Nature Neuroscience · doi:10.1038/nn2010 · Cited by 444 · see citing works
Yasui, D. H., Peddada, S., Bieda, M. C., Vallero, R. O., Hogart, A., Nagarajan, R. P., Thatcher, K. N., Farnham, P., & LaSalle, J. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707442104 · Cited by 381 · see citing works
Gardina, P. J., Clark, T. A., Shimada, B., Staples, M. K., Yang, Q., Veitch, J. M., Schweitzer, A. C., Awad, T. A., Sugnet, C. W., Dee, S., et al. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-325 · Cited by 352 · see citing works
Tudor, M., Akbarian, S., Chen, R. Z., & Jaenisch, R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242566899 · Cited by 343 · see citing works
MeCP2 dysfunction in Rett syndrome and related disorders
Moretti, P. M., & Zoghbi, H. Y. (2006) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2006.04.009 · Cited by 290 · see citing works
Self-citationMartin, C. L., Duvall, J. A., Ilkin, Y., Simon, J. S., Arreaza, M. G., Wilkes, K., Alvarez‐Retuerto, A., Whichello, A., Powell, C. M., Rao, K., et al. (2007) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30530 · Cited by 198 · see citing works
Bhalla, K., Phillips, H. A., Crawford, J., McKenzie, O. L. D., Mulley, J. C., Eyre, H., Gardner, A. E., Kremmidiotis, G., & Callen, D. F. (2004) · Journal of Human Genetics · doi:10.1007/s10038-004-0145-4 · Cited by 146 · see citing works
Axelrod, F. B., Chelimsky, G. G., & Weese‐Mayer, D. E. (2006) · PEDIATRICS · doi:10.1542/peds.2005-3032 · Cited by 123 · see citing works
Detection and measurement of alternative splicing using splicing-sensitive microarrays
Srinivasan, K., Shiue, L., Hayes, J. D., Centers, R., Fitzwater, S. P., Loewen, R., Edmondson, L. R., Bryant, J., Smith, M., & Rommelfanger, C. (2005) · Methods · doi:10.1016/j.ymeth.2005.09.007 · Cited by 101 · see citing works
Biochemical and clinical characteristics of creatine deficiency syndromes
Sykut-Cegielska, J., Gradowska, W., Mercimek-Mahmutoglu, S., & Stöckler-Ipsiroglu, S. (2004) · Acta Biochimica Polonica · doi:10.18388/abp.2004_3520 · Cited by 60 · see citing works
Caldeira, H., Smit, W., Verhoeven‐Duif, N. M., Salomons, G. S., Silva, S., Vasconcelos, R., Tomás, H., de Almeida, I. T., Jakobs, C., & Durán, M. (2005) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30226 · Cited by 59 · see citing works
Verbruggen, K. T., Knijff, W. A., Soorani-Lunsing, R. J., Sijens, P. E., Verhoeven, N. M., Salomons, G. S., Goorhuis-Brouwer, S. M., & van Spronsen, F. J. (2007) · European Journal of Pediatrics · doi:10.1007/s00431-006-0340-8 · Cited by 17 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [11]Srinivasan K, et al. Methods. 2005;37:345. [Google Scholar]
- [18]Sykut-Cegielska J, Gradowska W, Mercimek-Mahmutoglu S, Stockler-Ipsiroglu S. Acta Biochim Pol. 2004;51:875. [PubMed] [Google Scholar]
Cited by
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Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,949 · see citing works
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Portela, A., & Esteller, M. (2010) · Nature Biotechnology · doi:10.1038/nbt.1685 · Cited by 2,843 · see citing works
Burnside, R. D. (2015) · Cytogenetic and Genome Research · doi:10.1159/000438708 · Cited by 1,958 · see citing works
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Autry, A. E., & Monteggia, L. M. (2012) · Pharmacological Reviews · doi:10.1124/pr.111.005108 · Cited by 1,390 · see citing works
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 · see citing works
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Roth, T. L., Lubin, F. D., Funk, A. J., & Sweatt, J. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.028 · Cited by 1,273 · see citing works
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Mellén, M., Ayata, P., Dewell, S., Kriaucionis, S., & Heintz, N. (2012) · Cell · doi:10.1016/j.cell.2012.11.022 · Cited by 943 · see citing works
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Swiech, L., Heidenreich, M., Banerjee, A., Habib, N., Li, Y., Trombetta, J., Sur, M., & Zhang, F. (2015) · Nature Biotechnology · doi:10.1038/nbt.3055 · Cited by 772 · see citing works
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Yoshii, A., & Constantine‐Paton, M. (2010) · Developmental Neurobiology · doi:10.1002/dneu.20765 · Cited by 744 · see citing works
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Skene, P. J., Illingworth, R. S., Webb, S., Kerr, A. R. W., James, K. D., Turner, D. J., Andrews, R., & Bird, A. P. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.01.030 · Cited by 688 · see citing works
Greer, P. L., & Greenberg, M. E. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.002 · Cited by 661 · see citing works
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Tropea, D., Giacometti, E., Wilson, N. R., Beard, C., McCurry, C., Fu, D. D., Flannery, R., Jaenisch, R., & Sur, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812394106 · Cited by 593 · see citing works
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Gabel, H. W., Kinde, B., Stroud, H., Gilbert, C. S., Harmin, D. A., Kastan, N. R., Hemberg, M., Ebert, D. H., & Greenberg, M. E. (2015) · Nature · doi:10.1038/nature14319 · Cited by 569 · see citing works
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Gao, R., & Penzes, P. (2015) · Current Molecular Medicine · doi:10.2174/1566524015666150303003028 · Cited by 516 · see citing works
“Given the plethora of MeCP2 binding targets throughout the genome [236], it is particularly difficult to tease apart how MeCP2 specifically impairs inhibitory function [227].”
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Im, H., Hollander, J. A., Bali, P., & Kenny, P. J. (2010) · Nature Neuroscience · doi:10.1038/nn.2615 · Cited by 435 · see citing works
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Toro, R., Konyukh, M., Delorme, R., Leblond, C., Chaste, P., Fauchereau, F., Coleman, M., Leboyer, M., Gillberg, C., & Bourgeron, T. (2010) · Trends in Genetics · doi:10.1016/j.tig.2010.05.007 · Cited by 331 · see citing works
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Baroncelli, L., Braschi, C., Spolidoro, M., Begenisic, T., Sale, A., & Maffei, L. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2009.193 · Cited by 330 · see citing works
Roth, T. L., Zoladz, P. R., Sweatt, J. D., & Diamond, D. M. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.01.013 · Cited by 321 · see citing works
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Cuddapah, V. A., Pillai, R. B., Shekar, K. V., Lane, J. B., Motil, K. J., Skinner, S. A., Tarquinio, D. C., Glaze, D. G., McGwin, G., Kaufmann, W. E., et al. (2014) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2013-102113 · Cited by 311 · see citing works
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Sweatt, J. D. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.09.002 · Cited by 302 · see citing works
Chen, L., Chen, K., Lavery, L. A., Baker, S. A., Shaw, C. A., Li, W., & Zoghbi, H. Y. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1505909112 · Cited by 301 · see citing works
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Ramocki, M. B., Peters, S. U., Tavyev, Y. J., Zhang, F., Carvalho, C. M. B., Schaaf, C. P., Richman, R., Fang, P., Glaze, D. G., Lupski, J. R., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21715 · Cited by 302 · see citing works
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Oliveira, A. M. M., Hemstedt, T. J., & Bading, H. (2012) · Nature Neuroscience · doi:10.1038/nn.3151 · Cited by 289 · see citing works
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Maezawa, I., Swanberg, S. E., Harvey, D. J., LaSalle, J. M., & Jin, L. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0324-09.2009 · Cited by 283 · see citing works
Jameson, S. A., Natarajan, A., Cool, J., DeFalco, T., Maatouk, D. M., Mork, L., Munger, S. C., & Capel, B. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002575 · Cited by 287 · see citing works
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Sztainberg, Y., & Zoghbi, H. Y. (2016) · Nature Neuroscience · doi:10.1038/nn.4420 · Cited by 286 · see citing works
Self-citationFundamental Elements in Autism: From Neurogenesis and Neurite Growth to Synaptic Plasticity
Gilbert, J. P., & Man, H. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00359 · Cited by 274 · see citing works
Ortega-Martinez, S. (2015) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2015.00046 · Cited by 263 · see citing works
Epigenetic Mechanisms of Depression and Antidepressant Action
Vialou, V., Feng, J., Robison, A. J., & Nestler, E. J. (2013) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134540 · Cited by 277 · see citing works
HDAC4 Governs a Transcriptional Program Essential for Synaptic Plasticity and Memory
Sando, R., Gounko, N., Pieraut, S., Liao, L., Yates, J., & Maximov, A. (2012) · Cell · doi:10.1016/j.cell.2012.09.037 · Cited by 274 · see citing works
Cheung, A. Y. L., Horvath, L. M., Grafodatskaya, D., Pasceri, P., Weksberg, R., Hotta, A., Carrel, L., & Ellis, J. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr093 · Cited by 271 · see citing works
Adult Neural Function Requires MeCP2
McGraw, C. M., Samaco, R. C., & Zoghbi, H. Y. (2011) · Science · doi:10.1126/science.1206593 · Cited by 255 · see citing works
Self-citationLi, H., Radford, J. C., Ragusa, M. J., Shea, K. L., McKercher, S. R., Zaremba, J. D., Soussou, W., Nie, Z., Kang, Y., Nakanishi, N., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802876105 · Cited by 254 · see citing works
Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications
Jiang, C.-C., Lin, L., Long, S., Ke, X., Fukunaga, K., Lu, Y., & Han, F. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01081-0 · Cited by 272 · see citing works
Samaco, R. C., Mandel‐Brehm, C., Chao, H.-T., Ward, C. S., Fyffe-Maricich, S. L., Ren, J. T., Hyland, Κ., Christina Thaller, B., Maricich, S. M., Humphreys, P., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912257106 · Cited by 254 · see citing works
Self-citationCheng, T.-L., Wang, Z., Liao, Q., Zhu, Y., Zhou, W.-H., Xu, W., & Qiu, Z. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.01.032 · Cited by 253 · see citing works
Fyffe, S. L., Neul, J. L., Samaco, R. C., Chao, H.-T., Ben-Shachar, S., Moretti, P., McGill, B. E., Goulding, E. H., Sullivan, E., Tecott, L. H., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.07.030 · Cited by 254 · see citing works
Self-citationChapleau, C. A., Calfa, G. D., Lane, M. C., Albertson, A. J., Larimore, J. L., Kudo, S., Armstrong, D. L., Percy, A. K., & Pozzo‐Miller, L. D. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.05.001 · Cited by 253 · see citing works
Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus
Ben-Shachar, S., Chahrour, M., Thaller, C., Shaw, C. A., & Zoghbi, H. Y. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp181 · Cited by 253 · see citing works
Self-citationGao, Z., Ure, K., Ding, P., Nashaat, M. A., Yuan, L., Ma, J., Hammer, R. E., & Hsieh, J. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1604-11.2011 · Cited by 248 · see citing works
Rett syndrome: insights into genetic, molecular and circuit mechanisms
Ip, J. P. K., Mellios, N., & Sur, M. (2018) · Nature reviews. Neuroscience · doi:10.1038/s41583-018-0006-3 · Cited by 247 · see citing works
Roth, T. L., & David Sweatt, J. (2011) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2010.02282.x · Cited by 246 · see citing works
Pontine Mechanisms of Respiratory Control
Dutschmann, M., & Dick, T. E. (2012) · Comprehensive physiology · doi:10.1002/cphy.c100015 · Cited by 266 · see citing works
Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett syndrome
Castro, J., Garcia, R. I., Kwok, S., Banerjee, A., Petravicz, J., Woodson, J., Mellios, N., Tropea, D., & Sur, M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1311685111 · Cited by 242 · see citing works
Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses
Goffin, D., Allen, M., Zhang, L., Amorim, M., Wang, I.-T. J., Reyes, A.-R. S., Mercado-Berton, A., Ong, C., Cohen, S., Hu, L., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.2997 · Cited by 226 · see citing works
Kinde, B., Gabel, H. W., Gilbert, C. S., Griffith, E. C., & Greenberg, M. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411269112 · Cited by 236 · see citing works
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons
Griesi-Oliveira, K., Acab, A., Gupta, A. R., Sunaga, D. Y., Chailangkarn, T., Nicol, X., Nunez, Y., Walker, M. F., Murdoch, J. D., Sanders, S. J., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.141 · Cited by 236 · see citing works
DNA methylation and childhood maltreatment: From animal models to human studies
Lutz, P.-E., & Turecki, G. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2013.07.069 · Cited by 236 · see citing works
Prenatal stress and epigenetics
Cao-Lei, L., de Rooij, S. R., King, S., Matthews, S. G., Metz, G. A. S., Roseboom, T. J., & Szyf, M. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.05.016 · Cited by 230 · see citing works
Autism: cause factors, early diagnosis and therapies
Bhat, S., Acharya, U. R., Adeli, H., Bairy, G. M., & Adeli, A. (2014) · Reviews in the Neurosciences · doi:10.1515/revneuro-2014-0056 · Cited by 235 · see citing works
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 · see citing works
A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome
Buchovecky, C. M., Turley, S. D., Brown, H. M., Kyle, S. M., McDonald, J. G., Liu, B., Pieper, A. A., Huang, W., Katz, D. M., Russell, D. W., et al. (2013) · Nature Genetics · doi:10.1038/ng.2714 · Cited by 234 · see citing works
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 · see citing works
Activity-dependent phosphorylation of MeCP2 threonine 308 regulates interaction with NCoR
Ebert, D. H., Gabel, H. W., Robinson, N. D., Kastan, N. R., Hu, L. S., Cohen, S., Navarro, A. J., Lyst, M. J., Ekiert, R., Bird, A. P., et al. (2013) · Nature · doi:10.1038/nature12348 · Cited by 227 · see citing works
Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function
Tao, J., Hu, K., Chang, Q., Wu, H., Sherman, N. E., Martinowich, K., Klose, R. J., Schanen, C., Jaenisch, R., Wang, W., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811648106 · Cited by 226 · see citing works
Protein interactome reveals converging molecular pathways among autism disorders
Sakai, Y., Shaw, C. A., Dawson, B. C., Dugas, D. V., Al-Mohtaseb, Z., Hill, D. E., & Zoghbi, H. Y. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002166 · Cited by 226 · see citing works
Self-citation
- Authors
- Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T. C., Qin, J., & Zoghbi, H. Y.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Zoghbi, Huda Y.
- Venue
- Science
- Published
- 2008-05-30
- Volume
- 320
- Issue
- 5880
- Pages
- 1224-1229
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2443785
- OpenAlex
- W2039276157
- Cited by
- 1,823
- References
- 22
- Citations by year
- 2026: 53 · 2025: 55 · 2024: 76 · 2023: 67 · 2022: 84 · 2021: 95 · 2020: 96 · 2019: 90 · 2018: 69 · 2017: 131 · 2016: 133 · 2015: 113 · 2014: 131 · 2013: 153 · 2012: 128
- FWCI
- 66.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (NS057819, R01NS057819)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 024064, P30HD024064)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- MeCP2, Rett syndrome, transcriptional repression, transcriptional activation, CREB1, promoter binding, hypothalamus, gene expression profiling, neuropsychiatric disorders, neurodevelopmental disorders
- MeSH terms
- Animals, Disease Models, Animal, Gene Expression Regulation, Hypothalamic Diseases, Hypothalamus, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Nervous System Diseases, Protein Binding, Repressor Proteins, Transcription Factors, Rett Syndrome, Transcriptional Activation, Cyclic AMP Response Element-Binding Protein, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Mice, Methyl-CpG-Binding Protein 2
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