Genetic modifiers of MeCP2 function in Drosophila
Open accessAbstract
The levels of methyl-CpG-binding protein 2 (MeCP2) are critical for normal post-natal development and function of the nervous system. Loss of function of MeCP2, a transcriptional regulator involved in chromatin remodeling, causes classic Rett syndrome (RTT) as well as other related conditions characterized by autism, learning disabilities, or mental retardation. Increased dosage of MeCP2 also leads to clinically similar neurological disorders and mental retardation. To identify molecular mechanisms capable of compensating for altered MeCP2 levels, we generated transgenic Drosophila overexpressing human MeCP2. We find that MeCP2 associates with chromatin and is phosphorylated at serine 423 in Drosophila, as is found in mammals. MeCP2 overexpression leads to anatomical (i.e., disorganized eyes, ectopic wing veins) and behavioral (i.e., motor dysfunction) abnormalities. We used a candidate gene approach to identify genes that are able to compensate for abnormal phenotypes caused by MeCP2 increased activity. These genetic modifiers include other chromatin remodeling genes (Additional sex combs, corto, osa, Sex combs on midleg, and trithorax), the kinase tricornered, the UBE3A target pebble, and Drosophila homologues of the MeCP2 physical interactors Sin3a, REST, and N-CoR. These findings demonstrate that anatomical and behavioral phenotypes caused by MeCP2 activity can be ameliorated by altering other factors that might be more amenable to manipulation than MeCP2 itself.
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?
There is evidence that NCoR can interact directly with methyl-binding proteins or indirectly via its interaction with the Sin3 corepressor complex.
“Although numerous corepressors have been identified that interact with methyl-binding proteins, there is evidence that NCoR can interact directly with methyl-binding proteins (22)(23)(24) or indirectly via its interaction with the Sin3 corepressor complex (36).”
From The Nuclear Receptor Corepressor Has Organizational Effects within the Developing Amygdala on Juvenile Social Play and Anxiety-Like Behavior (2010) · cites this paper as [23]
The Discussion (page unavailable) says MeCP2 associates with a corepressor complex containing Sin3A. The Results identify a Drosophila N-CoR homolog as a genetic modifier of MeCP2, but our copy does not say that N-CoR interacts with Sin3A or reaches MeCP2 indirectly through that complex. (LLM, conf=0.78)
Experimental — accuracy not yet measuredNCoR can also repress gene expression via its interactions with methyl-binding proteins, such as Kaiso and MeCP2.
“Given that NCoR disruption increases juvenile anxiety-like behavior in both males and females, it is important to consider that NCoR can also repress gene expression via its interactions with methyl-binding proteins, such as Kaiso (22) and MeCP2 (23,24).”
From The Nuclear Receptor Corepressor Has Organizational Effects within the Developing Amygdala on Juvenile Social Play and Anxiety-Like Behavior (2010) · cites this paper as [23]
MeCP2 has been shown to directly interact with Sin3a and Rest as well as NCoR, and it has been suggested that these proteins may be better therapeutic targets than MeCP2.
“Recently, MeCP2 has been shown to directly interact with Sin3a and Rest as well as NCoR, and it has been suggested that these proteins may be better therapeutic targets than MeCP2 (23).”
From The Nuclear Receptor Corepressor Has Organizational Effects within the Developing Amygdala on Juvenile Social Play and Anxiety-Like Behavior (2010) · cites this paper as [23]
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
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes
Brand, A. H., & Perrimon, N. (1993) · Development · doi:10.1242/dev.118.2.401 · Cited by 9,510 · see citing works
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
MeCP2, 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
Self-citationA 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
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 · see citing works
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 · see citing works
Self-citationShilatifard, A. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142422 · Cited by 1,099 · see citing works
Epigenetic Regulation of Cellular Memory by the Polycomb and Trithorax Group Proteins
Ringrose, L., & Paro, R. (2004) · Annual Review of Genetics · doi:10.1146/annurev.genet.38.072902.091907 · Cited by 1,077 · 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
Self-citationPolycomb silencing mechanisms and the management of genomic programmes
Schwartz, Y. B., & Pirrotta, V. (2007) · Nature Reviews Genetics · doi:10.1038/nrg1981 · Cited by 868 · see citing works
De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome
Matsuura, T., Sutcliffe, J. S., Fang, P., Galjaard, R. H., Jiang, Y., Benton, C. S., Rommens, J. M., & Beaudet, A. L. (1997) · Nature Genetics · doi:10.1038/ng0197-74 · Cited by 858 · see citing works
Identification of genes that modify ataxin-1-induced neurodegeneration
Fernandez-Funez, P., Nino-Rosales, M. L., de Gouyon, B., She, W.-C., Luchak, J. M., Martinez, P., Turiegano, E., Benito, J., Capovilla, M., Skinner, P. J., et al. (2000) · Nature · doi:10.1038/35040584 · Cited by 661 · see citing works
Self-citationDNA methylation and chromatin modification
Ng, H.-H., & Adrian, B. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)80024-0 · Cited by 648 · see citing works
Esch, H. V., Bauters, M., Ignatius, J., Jansen, M., Raynaud, M., Hollanders, K., Lugtenberg, D., Bienvenu, T., Jensen, L. R., Gécz, J., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/444549 · Cited by 630 · 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-citationDissection of the methyl-CpG binding domain from the chromosomal protein MeCP2
Nan, X., Meehan, R. R., & Bird, A. P. (1993) · Nucleic Acids Research · doi:10.1093/nar/21.21.4886 · Cited by 605 · see citing works
DNA methylation in Drosophila melanogaster
Lyko, F., Ramsahoye, B. H., & Jaenisch, R. (2000) · Nature · doi:10.1038/35046205 · Cited by 501 · see citing works
Huntingtin Interacting Proteins Are Genetic Modifiers of Neurodegeneration
Kaltenbach, L. S., Romero, E., Becklin, R. R., Chettier, R., Bell, R. N., Phansalkar, A. R., Strand, A. D., Torcassi, C., Savage, J. R., Hurlburt, A. P., et al. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030082 · Cited by 430 · see citing works
Self-citationSamaco, R. C., Hogart, A., & LaSalle, J. M. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddi045 · Cited by 420 · see citing works
Corepressor-Dependent Silencing of Chromosomal Regions Encoding Neuronal Genes
Lunyak, V. V., Burgess, R., Prefontaine, G. G., Nelson, C., Sze, S.-H., Chenoweth, J., Schwartz, P., Pevzner, P. A., Glass, C., Mandel, G., et al. (2002) · Science · doi:10.1126/science.1076469 · Cited by 416 · see citing works
The methyl-CpG binding domain and the evolving role of DNA methylation in animals
Hendrich, B., & Tweedie, S. (2003) · Trends in Genetics · doi:10.1016/s0168-9525(03)00080-5 · Cited by 397 · 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
Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice
Luikenhuis, S., Giacometti, E., Beard, C., & Jaenisch, R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401626101 · Cited by 354 · see citing works
DNA Methylation Specifies Chromosomal Localization of MeCP2
Nan, X., Tate, P. H., Li, E., & Bird, A. P. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.1.414 · Cited by 343 · see citing works
DNA Binding Selectivity of MeCP2 Due to a Requirement for A/T Sequences Adjacent to Methyl-CpG
Klose, R. J., Sarraf, S. A., Schmiedeberg, L., McDermott, S. M., Stancheva, I., & Bird, A. P. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.07.021 · Cited by 339 · see citing works
Polycomb, Epigenomes, and Control of Cell Identity
Orlando, V. (2003) · Cell · doi:10.1016/s0092-8674(03)00157-0 · Cited by 339 · see citing works
Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing
Kaipananickal, H., Chow, M. Z. Y., Baker, E. K., Pal, S., Bassal, S., Brasacchio, D., Wang, L., Craig, J. M., Jones, P. L., Sif, S., et al. (2005) · Nature Genetics · doi:10.1038/ng1516 · Cited by 305 · see citing works
Chromatin Compaction by Human MeCP2
Georgel, P. T., Horowitz-Scherer, R. A., Adkins, N., Woodcock, C. L., Wade, P. A., & Hansen, J. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305308200 · Cited by 305 · see citing works
del Gaudio, D., Fang, P., Scaglia, F., Ward, P. A., Craigen, W. J., Glaze, D. G., Neul, J. L., Patel, A., Lee, J. A., Irons, M., et al. (2006) · Genetics in Medicine · doi:10.1097/01.gim.0000250502.28516.3c · Cited by 271 · see citing works
Self-citationFraga, M. F. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg249 · Cited by 238 · see citing works
Emoto, K., He, Y., Ye, B., Grueber, W. B., Adler, P. N., Jan, L. Y., & Jan, Y.-N. (2004) · Cell · doi:10.1016/j.cell.2004.09.036 · Cited by 235 · see citing works
Hanson, R. D., Hess, J. L., Yu, B., Ernst, P., van Lohuizen, M., Berns, A. J. M., van der Lugt, N. M. T., Shashikant, C. S., Ruddle, F. H., Seto, M., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.25.14372 · Cited by 235 · see citing works
Identification of MeCP2 mutations in a series of females with autistic disorder
Carney, R. M., Wolpert, C. M., Ravan, S. A., Shahbazian, M. D., Ashley‐Koch, A. E., Cuccaro, M. L., Vance, J. M., & Pericak‐Vance, M. A. (2003) · Pediatric Neurology · doi:10.1016/s0887-8994(02)00624-0 · Cited by 234 · see citing works
Meins, M., Lehmann, J., Gerresheim, F., Herchenbach, J., Hagedorn, M., Hameister, K., & Epplen, J. T. (2005) · Journal of Medical Genetics · doi:10.1136/jmg.2004.023804 · Cited by 220 · see citing works
Drosophila cholinergic neurons and processes visualized with Gal4/UAS–GFP
Salvaterra, P. M., & Kitamoto, T. (2001) · Gene Expression Patterns · doi:10.1016/s1567-133x(01)00011-4 · Cited by 219 · see citing works
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 · see citing works
Tsai, C., Kao, H., Yao, T., McKeown, M., & Evans, R. M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80365-2 · Cited by 218 · see citing works
Ellis, M. C., O’Neill, E., & Rubin, G. M. (1993) · Development · doi:10.1242/dev.119.3.855 · Cited by 217 · see citing works
Watson, P., Black, G. C. M., Ramsden, S., Barrow, M., Super, M., Kerr, B. A., & Clayton‐Smith, J. (2001) · Journal of Medical Genetics · doi:10.1136/jmg.38.4.224 · Cited by 210 · see citing works
Colantuoni, C., Jeon, O., Hyder, K., Chenchik, A. A., Khimani, A. H., Narayanan, V., Hoffman, E. P., Kaufmann, W. E., Naidu, S., & Pevsner, J. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0428 · Cited by 203 · see citing works
Up-regulation of glucocorticoid-regulated genes in a mouse model of Rett syndrome
Nuber, U. A., Kriaučionis, S., Roloff, T. C., Guy, J., Selfridge, J., Steinhoff, C., Schulz, R., Lipkowitz, B., Ropers, H., Holmes, M. C., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi229 · Cited by 185 · see citing works
Multiple Modes of Interaction between the Methylated DNA Binding Protein MeCP2 and Chromatin
Tv, N., Shi, X., Ghosh, R. P., Horowitz-Scherer, R. A., Hansen, J. C., & Woodcock, C. L. F. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01593-06 · Cited by 178 · see citing works
Rett Syndrome: A Prototypical Neurodevelopmental Disorder
Neul, J. L., & Zoghbi, H. Y. (2004) · The Neuroscientist · doi:10.1177/1073858403260995 · Cited by 166 · see citing works
Self-citationFunctional consequences of Rett syndrome mutations on human MeCP2
Yusufzai, T. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.21.4172 · Cited by 153 · see citing works
Makedonski, K., Abuhatzira, L., Kaufman, Y., Razin, A., & Shemer, R. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi097 · Cited by 130 · see citing works
Cerebellar gene expression profiles of mouse models for Rett syndrome reveal novel MeCP2 targets
Jordan, C., Li, H. H., Kwan, H. C. K., & Francke, U. (2007) · BMC Medical Genetics · doi:10.1186/1471-2350-8-36 · Cited by 126 · see citing works
DNA methylation and Rett syndrome
Kriaučionis, S., & Bird, A. P. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg286 · Cited by 125 · see citing works
Traynor, J., Agarwal, P., Lazzeroni, L. C., & Francke, U. (2002) · BMC Medical Genetics · doi:10.1186/1471-2350-3-12 · Cited by 109 · see citing works
Chicken MAR-Binding Protein ARBP Is Homologous to Rat Methyl-CpG-Binding Protein MeCP2
Weitzel, J. M., Buhrmester, H., & Strätling, W. H. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.9.5656 · Cited by 107 · see citing works
Expression of the Rho-GEF Pbl/ECT2 is regulated by the UBE3A E3 ubiquitin ligase
Reiter, L. T., Seagroves, T. N., Bowers, M., & Bier, E. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl225 · Cited by 102 · see citing works
Branco, J., Al‐Ramahi, I., Ukani, L., Perez, A. M., Fernández-Fúnez, P., Rincón-Limas, D. E., & Botas, J. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm315 · Cited by 74 · see citing works
Self-citationBalanced X chromosome inactivation patterns in the Rett syndrome brain
Shahbazian, M. D., Sun, Y., & Zoghbi, H. Y. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10557 · Cited by 73 · see citing works
Self-citationNeuronal Functions of the Novel Serine/Threonine Kinase Ndr2
Stork, O., Zhdanov, A., Kudersky, A., Yoshikawa, T., Obata, K., & Pape, H.-C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403552200 · Cited by 55 · see citing works
Pennetta, G., & Pauli, D. (1998) · Development Genes and Evolution · doi:10.1007/s004270050212 · Cited by 52 · see citing works
Expression profiling of clonal lymphocyte cell cultures from Rett syndrome patients
Delgado, I. J., Kim, D. S., Thatcher, K. N., LaSalle, J. M., & den Veyver, I. B. V. (2006) · BMC Medical Genetics · doi:10.1186/1471-2350-7-61 · Cited by 41 · see citing works
Ube3a expression is not altered in Mecp2 mutant mice
Jordan, C., & Francke, U. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl146 · Cited by 36 · see citing works
Another Patient With MECP2 Mutation Without Classic Rett Syndrome Phenotype
Milani, D., Pantaleoni, C., D’Arrigo, S., Selicorni, A., & Riva, D. (2005) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2004.12.012 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Epigenetics of Sex Differences in the Brain: Figure 1.
McCarthy, M. M., Auger, A. P., Bale, T. L., Vries, G. J. D., Dunn, G. A., Forger, N. G., Murray, E. K., Nugent, B. M., Schwarz, J. M., & Wilson, M. E. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3331-09.2009 · Cited by 478 · 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
Genetic Modifiers and Rare Mendelian Disease
Rahit, K. M. T. H., & Tarailo‐Graovac, M. (2020) · Genes · doi:10.3390/genes11030239 · Cited by 171 · see citing works
ATP-dependent chromatin remodeling in neural development
Yoo, A. S. J., & Crabtree, G. R. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.04.006 · Cited by 150 · see citing works
Genetic aspects of autism spectrum disorders: insights from animal models
Banerjee, S., Riordan, M., & Bhat, M. A. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00058 · Cited by 137 · see citing works
Iyer, J. S., Wang, Q., Le, T., Pizzo, L., Grönke, S., Ambegaokar, S. S., Imai, Y., Srivastava, A., Troisí, B. L., Mardon, G., et al. (2016) · G3 Genes Genomes Genetics · doi:10.1534/g3.116.027060 · Cited by 88 · see citing works
Hosking, B. M., François, M., Wilhelm, D., Orsenigo, F., Caprini, A., Svingen, T., Tutt, D. A. R., Davidson, T., Browne, C. M., Dejana, E., et al. (2009) · Development · doi:10.1242/dev.034827 · Cited by 87 · see citing works
Maes, T., Mascaró, C., Ortega, A., Lunardi, S., Ciceri, F., Somervaille, T. C. P., & Buesa, C. (2015) · Epigenomics · doi:10.2217/epi.15.9 · Cited by 86 · see citing works
Iyer, J. S., Singh, M. D., Jensen, M., Patel, P. T., Pizzo, L., Huber, E., Koerselman, H., Weiner, A. T., Lepanto, P., Vadodaria, K., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04882-6 · Cited by 80 · see citing works
Who’s in charge? Nuclear receptor coactivator and corepressor function in brain and behavior
Tetel, M. J., Auger, A. P., & Charlier, T. D. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.04.008 · Cited by 83 · see citing works
Novel variants identified in methyl-CpG-binding domain genes in autistic individuals
Cukier, H. N., Rabionet, R., Konidari, I., Rayner‐Evans, M. Y., Baltos, M. L., Wright, H. H., Abramson, R. K., Martin, E. R., Cuccaro, M. L., Pericak‐Vance, M. A., et al. (2009) · Neurogenetics · doi:10.1007/s10048-009-0228-7 · Cited by 77 · see citing works
Self-citationYin, J., & Schaaf, C. P. (2016) · Prenatal Diagnosis · doi:10.1002/pd.4942 · Cited by 68 · see citing works
Sex‐specific expression of estrogen receptors α and β and Kiss1 in the postnatal rat amygdala
Cao, J., & Patisaul, H. B. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23185 · Cited by 67 · see citing works
Jessen, H. M., & Auger, A. (2011) · Epigenetics · doi:10.4161/epi.6.7.16517 · Cited by 68 · see citing works
Drosophila models of early onset cognitive disorders and their clinical applications
van der Voet, M., Nijhof, B., Oortveld, M. A. W., & Schenck, A. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.01.013 · Cited by 62 · see citing works
Rett Syndrome: From Bed to Bench
Weng, S.-M., Bailey, M. E. S., & Cobb, S. (2011) · Pediatrics & Neonatology · doi:10.1016/j.pedneo.2011.08.002 · Cited by 61 · see citing works
Drosophila modeling of heritable neurodevelopmental disorders
Gatto, C. L., & Broadie, K. S. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.04.009 · Cited by 61 · see citing works
Epigenetic Modification of the Norepinephrine Transporter Gene in Postural Tachycardia Syndrome
Bayles, R., KN, H., Lambert, E., Baker, E. K., Agrotis, A., Guo, L., Jowett, J. B. M., Esler, M., Lambert, G., & El-Osta, A. (2012) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.111.244343 · Cited by 56 · see citing works
Jessen, H. M., Kolodkin, M. H., Bychowski, M. E., Auger, C. J., & Auger, A. P. (2010) · Endocrinology · doi:10.1210/en.2009-0594 · Cited by 53 · see citing works
Drosophila Glia: Models for Human Neurodevelopmental and Neurodegenerative Disorders
Kim, T., Song, B., & Lee, I. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144859 · Cited by 55 · 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
Neuroactive steroids: an update of their roles in central and peripheral nervous system.
Melcangi, R., & Panzica, G. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.11.001 · Cited by 47 · see citing works
Singh, M. D., Jensen, M., Lasser, M. C., Huber, E., Yusuff, T., Pizzo, L., Lifschutz, B., Desai, I., Kubina, A., Yennawar, S., et al. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008590 · Cited by 45 · see citing works
Epigenetic organization of brain sex differences and juvenile social play behavior
Auger, A. P., Jessen, H. M., & Edelmann, M. N. (2010) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.06.017 · 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
NET silencing by let-7i in postural tachycardia syndrome
Khan, A. W., Ziemann, M., Corcoran, S. J., Kaipananickal, H., Okabe, J., Rafehi, H., Maxwell, S., Esler, M., & El‐Osta, A. (2017) · JCI Insight · doi:10.1172/jci.insight.90183 · Cited by 37 · see citing works
Transcriptional regulation in pluripotent stem cells by methyl CpG-binding protein 2 (MeCP2).
Tanaka, Y., Kim, K.-Y., Zhong, M., Pan, X., Weissman, S., & Park, I.-H. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt500 · Cited by 35 · see citing works
Sexually Selected Traits: A Fundamental Framework for Studies on Behavioral Epigenetics
Jašarević, E., Geary, D. C., & Rosenfeld, C. S. (2012) · ILAR Journal · doi:10.1093/ilar.53.3-4.253 · Cited by 34 · see citing works
Drosophila as a Model for MECP2 Gain of Function in Neurons
Vonhoff, F., Williams, A. A., Ryglewski, S., & Duch, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031835 · Cited by 33 · see citing works
Kaipananickal, H., Bayles, R., Ciccotosto, G. D., Maxwell, S., Cappai, R., Pelka, G. J., Tam, P., Christodoulou, J., & El‐Osta, A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4675-09.2010 · Cited by 31 · see citing works
Park, S. M., Littleton, J. T., Park, H. R., & Lee, J. (2016) · Experimental Neurobiology · doi:10.5607/en.2016.25.1.33 · Cited by 27 · see citing works
Ube3a/E6AP is involved in a subset of MeCP2 functions
Kim, S., Chahrour, M. H., Ben‐Shachar, S., & Lim, J. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.06.036 · Cited by 23 · see citing works
Corepressors, nuclear receptors, and epigenetic factors on DNA: A tail of repression
Auger, A. P., & Jessen, H. M. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.05.012 · Cited by 21 · see citing works
MeCP2 Dysfunction in Rett Syndrome and Neuropsychiatric Disorders
Chin, E., & Goh, E. L. K. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9554-7_33 · Cited by 20 · see citing works
Functional conservation of MBD proteins: MeCP2 and Drosophila MBD proteins alter sleep
Gupta, T., Morgan, H. R., Bailey, J. A., & Certel, S. J. (2016) · Genes Brain & Behavior · doi:10.1111/gbb.12314 · Cited by 15 · see citing works
Machine Learning Representation of Loss of Eye Regularity in a Drosophila Neurodegenerative Model
Diez‐Hermano, S., Ganfornina, M. D., Vegas, E., & Sánchez, D. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00516 · Cited by 14 · see citing works
MeCP2 interacts with the super elongation complex to regulate transcription
Sonn, J. Y., Kim, W., Iwanaszko, M., Aoi, Y., Li, Y., Qi, G., Parkitny, L., Brissette, J. L., Weiner, L., Botas, J., et al. (2025) · Science Advances · doi:10.1126/sciadv.adt5937 · Cited by 14 · see citing works
Self-citationThe complexity of Rett syndrome models: Primary fibroblasts as a disease-in-a-dish reliable approach
Cordone, V., Pecorelli, A., Amicarelli, F., Hayek, J., & Valacchi, G. (2019) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2019.11.001 · Cited by 13 · see citing works
Yusuff, T., Jensen, M., Yennawar, S., Pizzo, L., Karthikeyan, S., Gould, D. J., Sarker, A., Gedvilaite, E., Matsui, Y., Iyer, J. S., et al. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008792 · Cited by 12 · see citing works
Astrocyte-specific regulation of hMeCP2 expression in Drosophila
Hess-Homeier, D. L., Fan, C.-Y., Gupta, T., Chiang, A., & Certel, S. J. (2014) · Biology Open · doi:10.1242/bio.20149092 · Cited by 12 · see citing works
Amodio, V., Tevy, M. F., Traina, C., Ghosh, T. K., & Capovilla, M. (2011) · Developmental Dynamics · doi:10.1002/dvdy.22763 · Cited by 11 · see citing works
MeCP2 and CTCF: enhancing the cross-talk of silencers
Ausió, J., & Georgel, P. T. (2017) · Biochemistry and Cell Biology · doi:10.1139/bcb-2017-0147 · Cited by 11 · see citing works
Khan, A. W., Corcoran, S. J., Esler, M., & El-Osta, A. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.015 · Cited by 11 · see citing works
Genetic approaches in Drosophila for the study neurodevelopmental disorders
Okray, Z., & Hassan, B. A. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.09.007 · Cited by 9 · see citing works
Drosophila Cbp53E Regulates Axon Growth at the Neuromuscular Junction
Hagel, K. R., Beriont, J., & Tessier, C. R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0132636 · Cited by 9 · see citing works
Apoptotic Activity of MeCP2 Is Enhanced by C-Terminal Truncating Mutations
Williams, A. A., Mehler, V. J., Mueller, C., Vonhoff, F., White, R., & Duch, C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0159632 · Cited by 8 · see citing works
Signalling Pathways in Development and Human Disease: A Drosophila Wing Perspective
Molnar, C., Resnik-Docampo, M., Maria, F., Martín, M., Hevia, C. F., & de Celis, J. F. (2011) · InTech eBooks · doi:10.5772/23858 · Cited by 8 · see citing works
Chen, E., Schmitt, J., McIntosh, G., Young, B. P., Lian, T., Liu, J., Chen, K. K., Liston, J. B., MacDonald, L., Wang, B., et al. (2025) · Genetics · doi:10.1093/genetics/iyaf121 · Cited by 5 · see citing works
Genome studies at the PAG 2011 conference
Appels, R., Adelson, D. L., Moolhuijzen, P., Webster, H., Barrero, R. A., & Bellgard, M. (2011) · Functional & Integrative Genomics · doi:10.1007/s10142-011-0215-6 · Cited by 5 · see citing works
Ali, N. E., Tariq, N., Naz, G., Abalkhail, A., Kausar, T., Mazhar, I., Zia, S. K., Aqib, A. I., & Khan, N. U. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-10802-x · Cited by 4 · see citing works
Regulation of Intestinal Stem Cell Proliferation by Human Methyl-CpG-binding Protein-2 in Drosophila
Lee, S.-H., Kim, I.-J., Kim, J.-G., Park, J., Kim, Y.-S., Yamaguchi, M., Kim, C.-M., & Yoo, M. (2011) · Cell Structure and Function · doi:10.1247/csf.11027 · Cited by 4 · see citing works
MECP2 impairs neuronal structure by regulating KIBRA
Williams, A. A., White, R., Siniard, A. L., Corneveaux, J. J., Huentelman, M. J., & Duch, C. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.03.019 · Cited by 4 · see citing works
Deciphering the role of siRNA in anxiety and depression
Bale, R., & Doshi, G. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176868 · Cited by 3 · see citing works
Modeling Intellectual Disability in Drosophila
Androschuk, A., & Bolduc, F. V. (2015) · Neuromethods · doi:10.1007/978-1-4939-2709-8_14 · Cited by 3 · see citing works
Invertebrate Models of Synaptic Transmission in Autism Spectrum Disorders
Ruiz‐Rubio, M., Calahorro, F., & Gámez-del-Estal, M. M. (2014) · Neuromethods · doi:10.1007/978-1-4939-2250-5_6 · Cited by 3 · see citing works
Gualtieri, C., Smith, Z. M., Cruz, A., Khan, Z., Jenkins, C., Mishra-Gorur, K., & Vonhoff, F. (2025) · Biology · doi:10.3390/biology14091228 · Cited by 2 · see citing works
Neuroepigenetics of Sexual Differentiation of Brain and Behavior
McCarthy, M., Stockman, S. L., & Nugent, B. M. (2016) · Epigenetics and human health · doi:10.1007/978-3-319-24493-8_9 · Cited by 1 · see citing works
Weiner, L., & Brissette, J. L. (2022) · FEBS Journal · doi:10.1111/febs.16542 · Cited by 2 · see citing works
Drosophila as a Model for Human Diseases
Marcogliese, P. C., & Wangler, M. (2018) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0005578.pub2 · Cited by 3 · see citing works
Mok, J.-W., Gibson, S., Dostalik, H. A., & Yamamoto, S. (2025) · Genome Research · doi:10.1101/gr.278291.123 · Cited by 2 · see citing works
Auger, A. P. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-802114-9.00015-9 · Cited by 1 · see citing works
Chapter 5 – Perinatal Neurohormonal Programming and Endocrine Disruption
Rosenfeld, C. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801383-0.00005-0 · Cited by 1 · see citing works
Auger, A. P., & Auger, C. J. (2013) · Epigenetics and human health · doi:10.1007/978-3-642-36827-1_3 · Cited by 1 · see citing works
Epigenetic Contribution to Sex Differences in Brain and Behavior
Auger, A. P., & McCarthy, M. M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00093-6 · Cited by 1 · see citing works
Drosophila as a Neurotoxicological Model
Lawal, H. O., & Krantz, D. E. (2018) · Methods in pharmacology and toxicology · doi:10.1007/7653_2018_12 · Cited by 1 · see citing works
NCBP2 modulates neurodevelopmental defects of the 3q29 deletion in Drosophila and X. laevis modelsPreprint
Singh, M. D., Jensen, M., Lasser, M. C., Huber, E., Yusuff, T., Pizzo, L., Lifschutz, B., Desai, I., Kubina, A., Yennawar, S., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/614750 · Cited by 2 · see citing works
Swami, M. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2475
Ajjuri, R. R., Hall, M., Reiter, L., & O'Donnell, J. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-405195-9.00005-6
Lung Defects Contribute to Respiratory Symptoms in a Mecp2-mutant Mouse Model of Rett Syndrome
Vashi, N. (2021) · TSpace (University of Toronto)
Ganga, C., & Devitt, A. (2020) · Journal of Emerging Investigators · doi:10.59720/20-053
Consonni, G., Kozluca, M. K., Gagliani, M. C., Mineo, A., Cortese, K., Miguel‐Aliaga, I., Vignoli, A., Borghi, E., Galeone, A., & Vaccari, T. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.16.694631
Autobehaver: An AI-Based Pipeline for Animal Behavior AnalysisPreprint
O’Neill, R. S., Aviles, S., & Rusan, N. M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.12.724596
Autism: epidemiology, genetics, molecular mechanisms, clinical features, diagnosis, and management
Fan, R., Wang, Y., & Miao, T. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00613-2
- Authors
- Cukier, H. N., Perez, A. M., Collins, A. L., Zhou, Z., Zoghbi, H. Y., & Botas, J.
- Affiliations
- Baylor College of Medicine (US)
- Boston Children's Hospital (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Botas, Juan
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-09-05
- Volume
- 4
- Issue
- 9
- Pages
- e1000179
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC2518867
- OpenAlex
- W2034911119
- Cited by
- 73
- References
- 58
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 1 · 2022: 1 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 9 · 2015: 5 · 2014: 7 · 2013: 3 · 2012: 5
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- University of Minnesota
- National Institutes of Health (5f31gm067501-02)
- National Institute of General Medical Sciences (1 F31 GM067501-01A1, F31 GM067501, HD024064)
- National Institute of Neurological Disorders and Stroke (NS042179, NS057819, R00NS058391, R01NS042179, K99NS058391, R56NS042179, R01NS057819)
- National Institute of Child Health and Human Development (HD024064)
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- MeCP2, Rett syndrome, genetic modifiers, Drosophila, chromatin remodeling, UBE3A, pebbles, trithorax, obstructive sleep apnea, SIN3A, rest, NCoR, motor impairment, autism spectrum disorder, intellectual disability
- MeSH terms
- Animals, Chromatin, Drosophila, Humans, Microscopy, Electron, Scanning, Phenotype, Phosphorylation, Serine, Animals, Genetically Modified, Methyl-CpG-Binding Protein 2
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
