Activity-dependent phosphorylation of MeCP2 threonine 308 regulates interaction with NCoR
Open accessAbstract
Rett syndrome (RTT) is an X-linked human neurodevelopmental disorder with features of autism and severe neurological dysfunction in females. RTT is caused by mutations in methyl-CpG-binding protein 2 (MeCP2), a nuclear protein that, in neurons, regulates transcription, is expressed at high levels similar to that of histones, and binds to methylated cytosines broadly across the genome. By phosphotryptic mapping, we identify three sites (S86, S274 and T308) of activity-dependent MeCP2 phosphorylation. Phosphorylation of these sites is differentially induced by neuronal activity, brain-derived neurotrophic factor, or agents that elevate the intracellular level of 3',5'-cyclic AMP (cAMP), indicating that MeCP2 may function as an epigenetic regulator of gene expression that integrates diverse signals from the environment. Here we show that the phosphorylation of T308 blocks the interaction of the repressor domain of MeCP2 with the nuclear receptor co-repressor (NCoR) complex and suppresses the ability of MeCP2 to repress transcription. In knock-in mice bearing the common human RTT missense mutation R306C, neuronal activity fails to induce MeCP2 T308 phosphorylation, suggesting that the loss of T308 phosphorylation might contribute to RTT. Consistent with this possibility, the mutation of MeCP2 T308A in mice leads to a decrease in the induction of a subset of activity-regulated genes and to RTT-like symptoms. These findings indicate that the activity-dependent phosphorylation of MeCP2 at T308 regulates the interaction of MeCP2 with the NCoR complex, and that RTT in humans may be due, in part, to the loss of activity-dependent MeCP2 T308 phosphorylation and a disruption of the phosphorylation-regulated interaction of MeCP2 with the NCoR complex.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The interaction between MeCP2 and the NCoR1/SMRT complex is facilitated by the NCoR1/SMRT interaction domain located at MeCP2 amino acids 285-309.
“Furthermore, this group found that the interaction between MeCP2 and the NCoR1/SMRT complex was facilitated by the NCoR1/SMRT interaction domain (NID) located at MeCP2 amino acids 285–309 [70,71].”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [71]
The main text reports that the region of MeCP2 surrounding T308 specifically mediates binding to the NCoR complex. However, the Methods (Peptide pull-down assays; page unavailable) identify the tested peptide as amino acids 285–319, not 285–309, and the cited passages do not establish 285–309 as the domain's boundaries or specifically name the SMRT complex. (LLM, conf=0.88)
Experimental — accuracy not yet measuredRTT dysfunction is caused by a failure of MECP2 to anchor the HDAC3/NCoR/SMRT complex to chromatin.
“suggest for the first time that RTT dysfunction is caused by a failure of MECP2 to anchor the HDAC3/NCoR/SMRT complex to chromatin53,54.”
From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [54]
The main text reports that an RTT-associated MeCP2 mutation disrupts binding to the NCoR complex, which includes HDAC3. But it says disrupted regulation of this interaction can lead to RTT-like symptoms—including when MeCP2 binds NCoR constitutively—and presents the proposed contribution to human RTT as a possibility. It does not establish failure to anchor the complex to chromatin as the cause of RTT dysfunction generally. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMeCP2 serves as a bridge between methylated DNA and the NCoR1/SMRT co-repressor complex, anchoring the complex to DNA via its NID and MBD.
“These findings have led to a model wherein MeCP2 serves as a bridge between methylated DNA and the corepressor complex, anchoring the NCoR1/SMRT complex to DNA via its NID and MBD, respectively.”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [71]
A subset of MECP2 missense mutations abolish interactions with a transcriptional co-repressor complex containing HDAC3, NCoR1, SMRT, and TBLR1.
“A subset of MECP2 missense mutations abolish interactions with a transcriptional co-repressor complex containing HDAC3, NCoR1, SMRT, and TBLR1.”
From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [54]
Such MECP2 missense mutations recapitulate Rett Syndrome phenotypes in mice.
“Such mutations recapitulate Rett Syndrome phenotypes in mice”
From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [54]
MeCP2 is a methyl-CpG binding protein involved in regulating neuronal chromatin architecture and gene transcription, especially in response to neural activity and experience after birth.
“M ECP2 is a methyl-CpG binding protein implicated in the regulation of neuronal chromatin architecture and gene transcription (1)(2)(3)(4), especially in response to neural activity and experience during postnatal life (5,6).”
From MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex (2015) · cites this paper as [6]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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 · see citing works
Nan, 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
Self-citationMeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T. C., Qin, J., & Zoghbi, H. Y. (2008) · Science · doi:10.1126/science.1153252 · Cited by 1,823 · see citing works
MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin.
Nan, X.-S., Campoy, F., & Bird, A. (1997) · Cell · doi:10.1016/s0092-8674(00)81887-5 · Cited by 1,403 · see citing works
Self-citationDerepression 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
Self-citationZhou, 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
Self-citationXia, Z., Dudek, H., Miranti, C. K., & Greenberg, M. E. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-17-05425.1996 · Cited by 794 · see citing works
Self-citationNeuronal MeCP2 Is Expressed at Near Histone-Octamer Levels and Globally Alters the Chromatin State
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
Self-citationActivity-dependent neuronal signalling and autism spectrum disorder
Ebert, D. H., & Greenberg, M. E. (2013) · Nature · doi:10.1038/nature11860 · Cited by 666 · see citing works
Self-citationActivity-dependent regulation of inhibitory synapse development by Npas4
Lin, Y., Bloodgood, B. L., Hauser, J. L., Lapan, A. D., Koon, A. C., Kim, T.-K., Hu, L. S., Malik, A. N., & Greenberg, M. E. (2008) · Nature · doi:10.1038/nature07319 · Cited by 639 · see citing works
Self-citationDani, V. S., Chang, Q., Maffei, A., Turrigiano, G. G., Jaenisch, R., & Nelson, S. B. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506071102 · Cited by 639 · see citing works
Both corepressor proteins SMRT and N‐CoR exist in large protein complexes containing HDAC3
Li, J., Wang, J., Wang, J., Nawaz, Z., Liu, J. M., Qin, J., & Wong, J. (2000) · The EMBO Journal · doi:10.1093/emboj/19.16.4342 · Cited by 629 · 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
Calmodulin-kinases: modulators of neuronal development and plasticity.
Wayman, G. A., Lee, Y.-S., Tokumitsu, H., Silva, A., & Soderling, T. R. (2008) · Neuron · doi:10.1016/j.neuron.2008.08.021 · Cited by 567 · see citing works
Deconstructing repression: evolving models of co-repressor action
Perissi, V., Jepsen, K., Glass, C. K., & Rosenfeld, M. G. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2736 · Cited by 532 · see citing works
Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor
Lyst, M. J., Ekiert, R., Ebert, D. H., Merusi, C., Nowak, J., Selfridge, J., Guy, J., Kastan, N. R., Robinson, N. D., de Lima Alves, F., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3434 · Cited by 410 · see citing works
Self-citationHong, E. J., McCord, A. E., & Greenberg, M. E. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.024 · Cited by 366 · see citing works
Self-citationThe MECP2 duplication syndrome
Ramocki, M. B., Tavyev, Y. J., & Peters, S. U. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33184 · Cited by 300 · see citing works
Cohen, S., Gabel, H. W., Hemberg, M., Hutchinson, A. N., Sadacca, L. A., Ebert, D. H., Harmin, D. A., Greenberg, R. S., Verdine, V. K., Zhou, Z., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.08.022 · Cited by 298 · see citing works
Self-citationMeCP2 Binding to DNA Depends upon Hydration at Methyl-CpG
Ho, K. L., McNae, I. W., Schmiedeberg, L., Klose, R. J., Bird, A. P., & Walkinshaw, M. D. (2008) · Molecular Cell · doi:10.1016/j.molcel.2007.12.028 · Cited by 282 · see citing works
Self-citationPhosphorylation 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
The Ski protein family is required for MeCP2-mediated transcriptional repression.
Kokura, K., Kaul, S. C., Wadhwa, R., Nomura, T., Khan, M. M., Shinagawa, T., Yasukawa, T., Colmenares, C., & Ishii, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105747200 · Cited by 222 · see citing works
Ballestar, E., Yusufzai, T. M., & Wolffe, A. P. (2000) · Biochemistry · doi:10.1021/bi0001271 · Cited by 169 · see citing works
Loss of activity-induced phosphorylation of MeCP2 enhances synaptogenesis, LTP and spatial memory
Li, H., Zhong, X., Chau, K. F., Williams, E. C., & Chang, Q. (2011) · Nature Neuroscience · doi:10.1038/nn.2866 · Cited by 153 · see citing works
Calcium Phosphate Transfection of DNA into Neurons in Primary Culture
Dudek, H., Ghosh, A., & Greenberg, M. E. (1998) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0311s03 · Cited by 29 · see citing works
Self-citationPhosphopeptide Mapping and Identification of Phosphorylation Sites
Meisenhelder, J., Hunter, T. R., & van der Geer, P. (1999) · Current Protocols in Protein Science · doi:10.1002/0471140864.ps1309s18 · Cited by 16 · see citing works
Phosphopeptide Mapping and Identification of Phosphorylation Sites
Meisenhelder, J., Hunter, T. R., & van der Geer, P. (1999) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb1809s48 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Editing DNA Methylation in the Mammalian Genome
Liu, X. S., Wu, H., Ji, X., Stelzer, Y., Wu, X., Czauderna, S., Shu, J., Dadon, D., Young, R. A., & Jaenisch, R. (2016) · Cell · doi:10.1016/j.cell.2016.08.056 · Cited by 1,224 · see citing works
From the genetic architecture to synaptic plasticity in autism spectrum disorder
Bourgeron, T. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3992 · Cited by 975 · see citing works
Activity-Regulated Transcription: Bridging the Gap between Neural Activity and Behavior
Yap, E.-L., & Greenberg, M. E. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.013 · Cited by 626 · see citing works
Self-citationDisruption of DNA-methylation-dependent long gene repression in Rett syndrome
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
Self-citationTet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction
Rudenko, A., Dawlaty, M. M., Seo, J., Cheng, A. W., Meng, J., Le, T. T., Faull, K. F., Jaenisch, R., & Tsai, L. (2013) · Neuron · doi:10.1016/j.neuron.2013.08.003 · Cited by 435 · see citing works
Spiegel, I., Mardinly, A. R., Gabel, H. W., Bazinet, J. E., Couch, C. H., Tzeng, C. P., Harmin, D. A., & Greenberg, M. E. (2014) · Cell · doi:10.1016/j.cell.2014.03.058 · Cited by 416 · see citing works
Self-citationRett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor
Lyst, M. J., Ekiert, R., Ebert, D. H., Merusi, C., Nowak, J., Selfridge, J., Guy, J., Kastan, N. R., Robinson, N. D., de Lima Alves, F., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3434 · Cited by 410 · see citing works
Self-citationDe novo genic mutations among a Chinese autism spectrum disorder cohort
Wang, T., Guo, H., Xiong, B., Stessman, H. A. F., Wu, H., Coe, B. P., Turner, T. N., Liu, Y., Zhao, W., Hoekzema, K., et al. (2016) · Nature Communications · doi:10.1038/ncomms13316 · Cited by 359 · see citing works
Epigenetics of Stress-Related Psychiatric Disorders and Gene × Environment Interactions
Klengel, T., & Binder, E. B. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.036 · Cited by 353 · see citing works
Rett syndrome: a complex disorder with simple roots
Lyst, M. J., & Bird, A. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3897 · Cited by 353 · see citing works
Self-citationCuddapah, 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
Li, Y., Wang, H., Muffat, J., Cheng, A. W., Orlando, D. A., Lovén, J., Kwok, S., Feldman, D., Bateup, H. S., Gao, Q., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.09.001 · Cited by 305 · 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
Cheng, 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
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
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
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
MECP2 disorders: from the clinic to mice and back
Lombardi, L. M., Baker, S. A., & Zoghbi, H. Y. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78167 · Cited by 221 · see citing works
Rett syndrome: a neurological disorder with metabolic components
Kyle, S. M., Vashi, N., & Justice, M. J. (2018) · Open Biology · doi:10.1098/rsob.170216 · Cited by 213 · see citing works
Epigenetics and the regulation of stress vulnerability and resilience
Zannas, A. S., & West, A. E. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2013.12.003 · Cited by 211 · see citing works
Clinical and biological progress over 50 years in Rett syndrome
Leonard, H., Cobb, S., & Downs, J. A. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.186 · Cited by 205 · see citing works
Integrative regulation of physiology by histone deacetylase 3
Emmett, M. J., & Lazar, M. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0076-0 · Cited by 202 · see citing works
Cronk, J. C., Derecki, N. C., Ji, E., Xu, Y., Lampano, A. E., Smirnov, I., Baker, W., Norris, G. T., Marin, I., Coddington, N., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.03.013 · Cited by 199 · see citing works
Histone deacetylases in memory and cognition
Penney, J., & Tsai, L. (2014) · Science Signaling · doi:10.1126/scisignal.aaa0069 · Cited by 192 · see citing works
The serotonin-BDNF duo: developmental implications for the vulnerability to psychopathology
Homberg, J. R., Molteni, R., Calabrese, F., & Riva, M. A. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.03.012 · Cited by 177 · see citing works
Liyanage, V. R. B., & Rastegar, M. (2014) · NeuroMolecular Medicine · doi:10.1007/s12017-014-8295-9 · Cited by 171 · see citing works
The Molecular Basis of MeCP2 Function in the Brain
Tillotson, R., & Bird, A. P. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.10.004 · Cited by 169 · see citing works
Self-citationGenomic patterns and context specific interpretation of DNA methylation
Baubec, T., & Schübeler, D. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.11.015 · Cited by 163 · see citing works
Radically truncated MeCP2 rescues Rett syndrome-like neurological defects
Tillotson, R., Selfridge, J., Koerner, M. V., Gadalla, K. K. E., Guy, J., De Sousa, D., Hector, R. D., Cobb, S. R., & Bird, A. (2017) · Nature · doi:10.1038/nature24058 · Cited by 155 · see citing works
Self-citationDNA Modifications: Function and Applications in Normal and Disease States
Liyanage, V. R. B., Jarmasz, J. S., Murugeshan, N., Bigio, M. R. D., Rastegar, M., & Davie, J. (2014) · Biology · doi:10.3390/biology3040670 · Cited by 150 · see citing works
Wachsmuth, M., Conrad, C., Bulkescher, J., Koch, B., Mahen, R., Isokane, M., Pepperkok, R., & Ellenberg, J. (2015) · Nature Biotechnology · doi:10.1038/nbt.3146 · Cited by 149 · see citing works
Krishnan, K., Wang, B.-S., Lu, J., Wang, L., Maffei, A., Cang, J., & Huang, Z. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1506499112 · Cited by 146 · see citing works
MeCP2: The Genetic Driver of Rett Syndrome Epigenetics
Good, K., Vincent, J. B., & Ausió, J. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.620859 · Cited by 143 · see citing works
Epigenetic Regulations in Neuropsychiatric Disorders
Kuehner, J. N., Bruggeman, E. C., Wen, Z., & Yao, B. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00268 · Cited by 137 · see citing works
Chromatin remodeling inactivates activity genes and regulates neural coding
Yang, Y., Yamada, T., Hill, K. K., Hemberg, M., Reddy, N. C., Cho, H. Y., Guthrie, A. N., Oldenborg, A., Heiney, S. A., Ohmae, S., et al. (2016) · Science · doi:10.1126/science.aad4225 · Cited by 123 · see citing works
Characterization of human mosaic Rett syndrome brain tissue by single-nucleus RNA sequencing
Renthal, W. R., Boxer, L. D., Hrvatin, S., Li, E., Silberfeld, A., Nagy, M. A., Griffith, E. C., Vierbuchen, T., & Greenberg, M. E. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0270-6 · Cited by 120 · see citing works
Self-citationWang, Y., Chen, L., Zhang, M., Li, X., Yang, X., Huang, T., Ban, Y., Li, Y., Li, Q., Zheng, Y., et al. (2023) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2023.05.009 · Cited by 117 · see citing works
Treating Rett syndrome: from mouse models to human therapies
Vashi, N., & Justice, M. J. (2019) · Mammalian Genome · doi:10.1007/s00335-019-09793-5 · Cited by 111 · see citing works
Histone deacetylase 3 associates with MeCP2 to regulate FOXO and social behavior
Nott, A., Cheng, J., Gao, F., Lin, Y.-T., Gjoneska, E., Ko, T., Minhas, P., Zamudio, A. V., Meng, J., Zhang, F., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4347 · Cited by 110 · see citing works
Towards a better diagnosis and treatment of Rett syndrome: a model synaptic disorder
Banerjee, A., Miller, M. T., Li, K., Sur, M., & Kaufmann, W. E. (2018) · Brain · doi:10.1093/brain/awy323 · Cited by 109 · see citing works
Epigenetic modifications in the nervous system and their impact upon cognitive impairments
Rudenko, A., & Tsai, L. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.01.043 · Cited by 108 · see citing works
Bellini, E., Pavesi, G., Barbiero, I., Bergo, A., Chandola, C., Nawaz, M., Rusconi, L., Stefanelli, G., Strollo, M., Valente, M. M., et al. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00236 · Cited by 97 · see citing works
Heckman, L. D., Chahrour, M. H., & Zoghbi, H. Y. (2014) · eLife · doi:10.7554/elife.02676 · Cited by 96 · see citing works
MeCP2: A Critical Regulator of Chromatin in Neurodevelopment and Adult Brain Function
Karaca, K. G., Brito, D. V. C., & Oliveira, A. M. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184577 · Cited by 95 · see citing works
MECP2 regulates cortical plasticity underlying a learned behaviour in adult female mice
Krishnan, K., Lau, B. Y. B., Ewall, G., Huang, Z. J., & Shea, S. D. (2017) · Nature Communications · doi:10.1038/ncomms14077 · Cited by 94 · see citing works
The Genetics of Autism Spectrum Disorders
Huguet, G., Benabou, M., & Bourgeron, T. (2016) · Research and perspectives in endocrine interactions · doi:10.1007/978-3-319-27069-2_11 · Cited by 94 · see citing works
Filippis, B. D., Valenti, D., Lidia de, B. A. R. I., Rasmo, D. D., Musto, M., Fabbri, A., Ricceri, L., Fiorentini, C., Laviola, G., & Vacca, R. A. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.02.014 · Cited by 90 · see citing works
Rett syndrome – biological pathways leading from MECP2 to disorder phenotypes
Ehrhart, F., Coort, S. L., Cirillo, E., Smeets, E., Evelo, C. T., & Curfs, L. (2016) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-016-0545-5 · Cited by 89 · see citing works
Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons
Xiang, Y., Tanaka, Y., Patterson, B., Hwang, S., Hysolli, E., Çakır, B., Kim, K., Wang, W., Kang, Y., Clement, E. M., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.05.016 · Cited by 88 · see citing works
MeCP2 Repression of G9a in Regulation of Pain and Morphine Reward
Zhang, Z., Tao, W., Hou, Y.-Y., Wang, W., Kenny, P. J., & Pan, Z. Z. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4194-13.2014 · Cited by 88 · see citing works
Inhibitors of DNA Methylation, Histone Deacetylation, and Histone Demethylation
Zahnow, C. A., Topper, M. J., Stone, M. L., Stewart, T. M., Li, H., Baylin, S. B., & Casero, R. A. (2016) · Advances in cancer research · doi:10.1016/bs.acr.2016.01.007 · Cited by 86 · see citing works
MeCP2 co-ordinates liver lipid metabolism with the NCoR1/HDAC3 corepressor complex
Kyle, S. M., Saha, P. K., Brown, H. M., Chan, L. C., & Justice, M. J. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw156 · Cited by 84 · see citing works
Rett Syndrome and MECP2 Duplication Syndrome: Disorders of MeCP2 Dosage
Collins, B. E., & Neul, J. L. (2022) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s371483 · Cited by 83 · see citing works
Methyl-CpG-binding 2 K271 lactylation-mediated M2 macrophage polarization inhibits atherosclerosis
Chen, L., Zhang, M., Yang, X., Wang, Y., Huang, T., Li, X., Ban, Y., Li, Q., Yang, Q., Zhang, Y., et al. (2024) · Theranostics · doi:10.7150/thno.94738 · Cited by 83 · see citing works
Kruusvee, V., Lyst, M. J., Taylor, C., Tarnauskaitė, Ž., Bird, A. P., & Cook, A. G. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700731114 · Cited by 82 · see citing works
Self-citationA High-Resolution Imaging Approach to Investigate Chromatin Architecture in Complex Tissues
Linhoff, M. W., Garg†, S. K., & Mandel, G. (2015) · Cell · doi:10.1016/j.cell.2015.09.002 · Cited by 82 · see citing works
Gold, W. A., Percy, A. K., Neul, J. L., Cobb, S., Pozzo‐Miller, L. D., Issar, J. K., Ben‐Zeev, B., Vignoli, A., & Kaufmann, W. E. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00568-0 · Cited by 80 · see citing works
Nuclear receptor corepressor complexes in cancer: mechanism, function and regulation.
Wong, M., Guo, C. H., & Zhang, J. (2014) · PubMed Central · Cited by 79 · see citing works
study, D., Zhou, W., He, Y., Rehman, A. U., Kong, Y., Hong, S., Ding, G., Yalamanchili, H. K., Wan, Y., Paul, B., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0311-1 · Cited by 77 · see citing works
Veley, K. M., Maksaev, G. I., Frick, E. M., January, E., Kloepper, S. C., & Haswell, E. S. (2014) · The Plant Cell · doi:10.1105/tpc.114.128082 · Cited by 77 · see citing works
Tai, D. J. C., Liu, Y., Hsu, W., Ma, Y., Cheng, S. J., Liu, S. Y., & Lee, E. H. Y. (2016) · Nature Communications · doi:10.1038/ncomms10552 · Cited by 73 · see citing works
The Crucial Role of DNA Methylation and MeCP2 in Neuronal Function
Fasolino, M., & Zhou, Z. (2017) · Genes · doi:10.3390/genes8050141 · Cited by 71 · see citing works
Li, H., Zhong, X., Chau, K. F., Santistevan, N. J., Guo, W., Kong, G., Li, X., Kadakia, M. B., Masliah, J., Chi, J., et al. (2014) · Nature Communications · doi:10.1038/ncomms6601 · Cited by 66 · see citing works
Pohodich, A. E., Yalamanchili, H. K., Raman, A. T., Wan, Y., Gundry, M. C., Hao, S., Jin, H., Tang, J., Liu, Z., & Zoghbi, H. Y. (2018) · eLife · doi:10.7554/elife.34031 · Cited by 65 · see citing works
Regulation of mRNA splicing by MeCP2 via epigenetic modifications in the brain
Cheng, T., Chen, J., Wan, H., Tang, B., Tian, W., Liao, L., & Qiu, Z. (2017) · Scientific Reports · doi:10.1038/srep42790 · Cited by 62 · see citing works
Epilepsy in Rett syndrome—Lessons from the Rett networked database
Nissenkorn, A., Levy‐Drummer, R. S., Bondi, O., Renieri, A., Villard, L., Mari, F., Mencarelli, M. A., Rizzo, C. L., Meloni, I., Pineda, M., et al. (2015) · Epilepsia · doi:10.1111/epi.12941 · Cited by 61 · see citing works
Bridging Rapid and Sustained Antidepressant Effects of Ketamine
Kim, J.-W., Suzuki, K., Kavalali, E. T., & Monteggia, L. M. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.02.003 · Cited by 59 · see citing works
Evolutionary and functional perspectives on signaling from neuronal surface to nucleus
Cohen, S. M., Li, B., Tsien, R. W., & Ma, H. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.02.146 · Cited by 55 · see citing works
Self-citationGene regulatory mechanisms underlying sex differences in brain development and psychiatric disease
Manoli, D. S., & Tollkühn, J. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13564 · Cited by 54 · see citing works
Real‐Time Monitoring of Phosphorylation Kinetics with Self‐Assembled Nano‐oscillators
Fang, Y., Chen, S., Wang, W., Shan, X., & Tao, N. J. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201411040 · Cited by 53 · see citing works
Brain-Derived Neurotrophic Factor and Rett Syndrome
Katz, D. M. (2014) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-45106-5_18 · Cited by 53 · see citing works
Ludwig, A. K., Zhang, P., & Cardoso, M. C. (2016) · Frontiers in Genetics · doi:10.3389/fgene.2016.00115 · Cited by 52 · see citing works
Rett syndrome and the urge of novel approaches to study MeCP2 functions and mechanisms of action
Bedogni, F., Rossi, R. L., Galli, F., Cobolli Gigli, C., Gandaglia, A., Kilstrup-Nielsen, C., & Landsberger, N. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.01.011 · Cited by 51 · see citing works
MeCP2: multifaceted roles in gene regulation and neural development
Cheng, T., & Qiu, Z. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-014-1452-6 · Cited by 50 · see citing works
MeCP2 Phosphorylation Limits Psychostimulant-Induced Behavioral and Neuronal Plasticity
Deng, J. V., Wan, Y., Wang, X., Cohen, S., Wetsel, W. C., Greenberg, M. E., Kenny, P. J., Calakos, N., & West, A. E. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2821-13.2014 · Cited by 49 · see citing works
Self-citationAusió, J. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0214-5 · Cited by 48 · see citing works
MeCP2 and Chromatin Compartmentalization
Schmidt, A., Zhang, H., & Cardoso, M. C. (2020) · Cells · doi:10.3390/cells9040878 · Cited by 48 · see citing works
MeCP2-Related Diseases and Animal Models
Ezeonwuka, C. D., & Rastegar, M. (2014) · Diseases · doi:10.3390/diseases2010045 · Cited by 48 · see citing works
Osenberg, S., Karten, A., Sun, J., Li, J., Charkowick, S. V., Felice, C. A., Kritzer, M. F., Nguyen, M. V. C., Yu, P., & Ballas, N. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1722546115 · Cited by 46 · see citing works
Altered motor learning and coordination in mouse models of autism spectrum disorder
Cording, K. R., & Bateup, H. S. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1270489 · Cited by 45 · see citing works
Azad, G. K., Ito, K., Sailaja, B. S., Biran, A., Nissim‐Rafinia, M., Yamada, Y., Brown, D. T., Takizawa, T., & Meshorer, E. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201703141 · Cited by 45 · see citing works
Chromatin-dependent allosteric regulation of DNMT3A activity by MeCP2
Rajavelu, A., Lungu, C., Emperle, M., Dukatz, M., Bröhm, A., Broche, J., Hanelt, I., Parsa, E., Schiffers, S., Karnik, R., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky715 · Cited by 45 · see citing works
Binding of MBD proteins to DNA blocks Tet1 function thereby modulating transcriptional noise
Ludwig, A. K., Zhang, P., Hastert, F. D., Meyer, S., Rausch, C., Herce, H. D., Müller, U., Lehmkuhl, A., Hellmann, I., Trummer, C., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1197 · Cited by 44 · see citing works
Morello, N., Schina, R., Pilotto, F., Phillips, M. L., Melani, R., Plicato, O., Pizzorusso, T., Pozzo‐Miller, L. D., & Giustetto, M. (2018) · eNeuro · doi:10.1523/eneuro.0086-18.2018 · Cited by 44 · see citing works
Ray, B., Sokol, D. K., Maloney, B., & Lahiri, D. K. (2016) · Scientific Reports · doi:10.1038/srep26052 · Cited by 42 · see citing works
Synaptic plasticity and signaling in rett syndrome
Sala, G. D., & Pizzorusso, T. (2013) · Developmental Neurobiology · doi:10.1002/dneu.22114 · Cited by 41 · see citing works
MECP2 and the biology of MECP2 duplication syndrome
D’Mello, S. R. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15331 · Cited by 41 · see citing works
Neurotrophins and Their Receptors: BDNF’s Role in GABAergic Neurodevelopment and Disease
Caño, C. H.-D., Varela-Andrés, N., Cebrián-León, A., & Deogracias, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158312 · Cited by 40 · see citing works
A mutation-led search for novel functional domains in MeCP2
Guy, J., Alexander-Howden, B., FitzPatrick, L., DeSousa, D., Koerner, M. V., Selfridge, J., & Bird, A. P. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy159 · Cited by 40 · see citing works
Self-citationDeciphering MECP2-associated disorders: disrupted circuits and the hope for repair
Qiu, Z. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.09.004 · Cited by 39 · see citing works
NCOR1—a new player on the field of T cell development
Müller, L., Hainberger, D., Stolz, V., & Ellmeier, W. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.1ri0418-168r · Cited by 38 · see citing works
Astrocyte Transcriptome from the Mecp2308-Truncated Mouse Model of Rett Syndrome
Delépine, C., Nectoux, J., Letourneur, F., Baud, V., Chelly, J., Billuart, P., & Bienvenu, T. (2015) · NeuroMolecular Medicine · doi:10.1007/s12017-015-8363-9 · Cited by 37 · see citing works
Kucukkal, T. G., Yang, Y., Chapman, S. C., Cao, W., & Alexov, E. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15069670 · Cited by 36 · see citing works
Wood, K. H., Johnson, B. S., Welsh, S. A., Lee, J. Y., Cui, Y., Krizman, E. N., Brodkin, E. S., Blendy, J. A., Robinson, M. B., Bartolomei, M. S., et al. (2016) · Epigenomics · doi:10.2217/epi-2015-0004 · Cited by 35 · see citing works
The crux of Cux genes in neuronal function and plasticity
Weiss, L. A., & Nieto, M. (2018) · Brain Research · doi:10.1016/j.brainres.2018.02.044 · Cited by 35 · see citing works
Philippe, T. J., Vahid-Ansari, F., Donaldson, Z. R., François, B. L., Zahrai, A., Turcotte-Cardin, V., Daigle, M., James, J., Hen, R., Merali, Z., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-24167-8 · Cited by 35 · see citing works
Genome–Environment Interactions and Psychiatric Disorders
Peedicayil, J. (2023) · Biomedicines · doi:10.3390/biomedicines11041209 · Cited by 35 · see citing works
An RNA interference screen identifies druggable regulators of MeCP2 stability
Lombardi, L. M., Zaghlula, M., Sztainberg, Y., Baker, S. A., Klisch, T. J., Tang, A. A., Huang, E. J., & Zoghbi, H. Y. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf7588 · Cited by 35 · see citing works
Transcriptional co-repressors and memory storage
Schoch, H., & Abel, T. G. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.01.003 · Cited by 33 · see citing works
Synaptically Localized Transcriptional Regulators in Memory Formation
Uchida, S., & Shumyatsky, G. P. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.07.023 · Cited by 33 · see citing works
- Authors
- 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., & Greenberg, M. E.
- Affiliations
- Harvard University (US)
- Wellcome Centre for Cell Biology (GB)
- Corresponding author
- Greenberg, Michael E.
- ORCID
- Venue
- Nature
- Published
- 2013-07
- Volume
- 499
- Issue
- 7458
- Pages
- 341-345
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3922283
- OpenAlex
- W2081756408
- Cited by
- 227
- References
- 27
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 9 · 2023: 12 · 2022: 14 · 2021: 14 · 2020: 12 · 2019: 10 · 2018: 23 · 2017: 21 · 2016: 25 · 2015: 19 · 2014: 33 · 2013: 14
- FWCI
- 20.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Wellcome Trust (092076)
- National Institutes of Health (5r01ns048276-15)
- National Institute of Mental Health (K08MH090306, K08MH90306)
- National Institute of General Medical Sciences (T32GM007753)
- National Institute of Neurological Disorders and Stroke (R01-NS-048276)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- MeCP2, Rett syndrome, NCoR, nuclear receptor corepressor, transcriptional repression, neuronal activity, brain-derived neurotrophic factor, cyclic AMP, epigenetic regulation, knock-in mice, neurodevelopmental disorders
- MeSH terms
- Animals, Cells, Cultured, Humans, Mutation, Neurons, Phosphorylation, Threonine, Transcription, Genetic, Rett Syndrome, Mice, Methyl-CpG-Binding Protein 2, Co-Repressor Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
