The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Control of Cognition and Adaptive Behavior by the GLP/G9a Epigenetic Suppressor Complex
Open accessAbstract
The genetic basis of cognition and behavioral adaptation to the environment remains poorly understood. Here we demonstrate that the histone methyltransferase complex GLP/G9a controls cognition and adaptive responses in a region-specific fashion in the adult brain. Using conditional mutagenesis in mice, we show that postnatal, neuron-specific deficiency of GLP/G9a leads to derepression of numerous nonneuronal and neuron progenitor genes in adult neurons. This transcriptional alteration is associated with complex behavioral abnormalities, including defects in learning, motivation, and environmental adaptation. The behavioral changes triggered by GLP/G9a deficiency are similar to key symptoms of the human 9q34 mental retardation syndrome that is associated with structural alterations of the GLP/EHMT1 gene. The likely causal role of GLP/G9a in mental retardation in mice and humans suggests a key role for the GLP/G9a-controlled histone H3K9 dimethylation in regulation of brain function through maintenance of the transcriptional homeostasis in adult neurons.
Overview
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
Verification
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Researchers have reported that postnatal knockout of G9a reduced the anxiety phenotype in mice, while mutation or deletion of one copy of the GLP gene in humans leads to Kleefstra syndrome, characterized by social behavior impairment, impulsivity, aggression, and mental retardation (Schaefer et al., 2009).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Schaefer et al., 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The HMT complex G9a/G9a-like protein (GLP), composed of the HMT euchromatic histone-lysine N-methyltransferase 2 (EHMT2) or G9a and G9a-like protein (GLP or EHMT1), has been shown to be involved in the monomethylation and dimethylation of H3K9 (Schaefer et al., 2009).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Schaefer et al., 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Researchers have reported that postnatal knockout of G9a reduced the anxiety phenotype in mice, while mutation or deletion of one copy of the GLP gene in humans leads to Kleefstra syndrome, characterized by social behavior impairment, impulsivity, aggression, and mental retardation (Schaefer et al., 2009).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Schaefer et al., 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Thus, G9a/GLP seems to exert temporal effects on developmental histone methylation.”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Schaefer et al., 2009
Experimental — accuracy not yet measuredIn the citing paper
“No statistical methods were used to pre-determine sample sizes but our sample sizes are similar to those reported in previous publications19,31,95,99,108.”
From Epigenetic regulation of brain region-specific microglia clearance activity (2018) · cites this paper as [95]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756
Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., & Zhang, Y. (2002) · Science · doi:10.1126/science.1076997 · Cited by 3,775
An efficient recombination system for chromosome engineering in Escherichia coli
Yu, D., Ellis, H. M., Lee, E.-C., Jenkins, N. A., Copeland, N. G., & Court, D. L. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.100127597 · Cited by 1,688
Zhang, Y., & Reinberg, D. (2001) · Genes & Development · doi:10.1101/gad.927301 · Cited by 1,639
Tachibana, M., Sugimoto, K., Nozaki, M., Ueda, J., Ohta, T., Ohki, M., Fukuda, M., Takeda, N., Niida, H., Kato, H., et al. (2002) · Genes & Development · doi:10.1101/gad.989402 · Cited by 1,294
Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitionsPreprint
Bracken, A. P., Dietrich, N., Pasini, D., Hansen, K. H., & Helin, K. (2006) · Genes & Development · doi:10.1101/gad.381706 · Cited by 1,286
Partitioning and Plasticity of Repressive Histone Methylation States in Mammalian Chromatin
Peters, A. H. F. M., Kubicek, S., Mechtler, K., O’Sullivan, R. J., Derijck, A. A. H. A., Perez-Burgos, L., Kohlmaier, A., Opravil, S., Tachibana, M., Shinkai, Y., et al. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00477-5 · Cited by 1,208
Lee, E.-C., Yu, D., de Velasco, J. M., Tessarollo, L., Swing, D. A., Court, D. L., Jenkins, N. A., & Copeland, N. G. (2001) · Genomics · doi:10.1006/geno.2000.6451 · Cited by 1,180
High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP
Rodríguez, C. I., Buchholz, F., Galloway, J. L., Sequerra, R., Kasper, J. S., Ayala, R., Stewart, A. F., & Dymecki, S. M. (2000) · Nature Genetics · doi:10.1038/75973 · Cited by 1,162
A translational profiling approach for the molecular characterization of CNS cell types
Heiman, M., Schaefer, A., Gong, S., Peterson, J. D., Day, M., Ramsey, K. E., Suárez-Fariñas, M., Schwarz, C., Stephan, D. A., Surmeier, D. J., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.028 · Cited by 1,134
Self-citationGong, S., Doughty, M., Harbaugh, C. R., Cummins, A., Hatten, M. E., Heintz, N., & Gerfen, C. R. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2707-07.2007 · Cited by 977
The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3
Cao, R., & Zhang, Y. (2004) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2004.02.001 · Cited by 944
Application of a translational profiling approach for the comparative analysis of CNS cell types
Doyle, J. P., Dougherty, J. D., Heiman, M., Schmidt, E. F., Stevens, T. R., Ma, G., Bupp, S., Shrestha, P., Shah, R. D., Doughty, M. L., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.029 · Cited by 912
Self-citationTachibana, M., Ueda, J., Fukuda, M., Takeda, N., Ohta, T., Iwanari, H., Sakihama, T., Kodama, T., Hamakubo, T., & Shinkai, Y. (2005) · Genes & Development · doi:10.1101/gad.1284005 · Cited by 868
Rice, J. C., Briggs, S. D., Ueberheide, B. M., Barber, C. M., Shabanowitz, J., Hunt, D. F., Shinkai, Y., & Allis, C. D. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00479-9 · Cited by 849
Coordinated histone modifications mediated by a CtBP co-repressor complex
Shi, Y. G., Sawada, J.-I., Sui, G., Affar, E. B., Whetstine, J. R., Lan, F., Ogawa, H., Luke, M. P.-S., Nakatani, Y., & Shi, Y. (2003) · Nature · doi:10.1038/nature01550 · Cited by 821
A Complex with Chromatin Modifiers That Occupies E2F- and Myc-Responsive Genes in G 0 Cells
Ogawa, H., Ishiguro, K., Gaubatz, S., Livingston, D. M., & Nakatani, Y. (2002) · Science · doi:10.1126/science.1069861 · Cited by 785
Tachibana, M., Sugimoto, K., Fukushima, T., & Shinkai, Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101914200 · Cited by 784
Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement
Su, I.-H., Basavaraj, A., Krutchinsky, A. N., Hobert, O., Ullrich, A., Chait, B. T., & Tarakhovsky, A. (2002) · Nature Immunology · doi:10.1038/ni876 · Cited by 635
Self-citationCerebellar neurodegeneration in the absence of microRNAs
Schaefer, A., O'Carroll, D., Tan, C. L., Hillman, D., Sugimori, M., Llinas, R., & Greengard, P. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070823 · Cited by 498
Self-citationDichotomous Anatomical Properties of Adult Striatal Medium Spiny Neurons
Gertler, T. S., Chan, C. S., & Surmeier, D. J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2660-08.2008 · Cited by 495
Self-citationHirabayashi, Y., Suzki, N., Tsuboi, M., Endo, T. A., Toyoda, T., Shinga, J., Koseki, H., Vidal, M., & Gotoh, Y. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.021 · Cited by 462
The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation
Tahiliani, M., Mei, P., Fang, R., Leonor, T., Rutenberg, M. S., Shimizu, F., Li, J., Rao, A., & Shi, Y. G. (2007) · Nature · doi:10.1038/nature05823 · Cited by 429
Failure of neuronal homeostasis results in common neuropsychiatric phenotypes
Ramocki, M. B., & Zoghbi, H. Y. (2008) · Nature · doi:10.1038/nature07457 · Cited by 399
Kleefstra, T., Brunner, H. G., Amiel, J., Oudakker, A. R., Nillesen, W. M., Magee, A. C., Geneviève, D., Cormier‐Daire, V., Esch, H. V., Fryns, J., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/505693 · Cited by 395
Gene Expression Nervous System Atlas (GENSAT)
Heintz, N. (2004) · Nature Neuroscience · doi:10.1038/nn0504-483 · Cited by 323
A CamKIIα iCre BAC allows brain‐specific gene inactivation
Casanova, E., Fehsenfeld, S., Mantamadiotis, T., Lemberger, T., Greiner, E. F., Stewart, A. F., & Schütz, G. (2001) · genesis · doi:10.1002/gene.1078 · Cited by 293
Genetics and pathophysiology of mental retardation
Chelly, J., Khelfaoui, M., Francis, F., Beldjord, C., & Bienvenu, T. (2006) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201595 · Cited by 289
Localized Domains of G9a-Mediated Histone Methylation Are Required for Silencing of Neuronal Genes
Roopra, A., Qazi, R., Schoenike, B. A., Daley, T. J., & Morrison, J. F. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.05.026 · Cited by 286
Molecular and Comparative Genetics of Mental Retardation
Inlow, J. K., & Restifo, L. L. (2004) · Genetics · doi:10.1534/genetics.166.2.835 · Cited by 264
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
Kleefstra, T., van Zelst-Stams, W. A., Nillesen, W. M., Cormier-Daire, V, Houge, G., Foulds, N., van Dooren, M., Willemsen, M. H., Pfundt, R., Turner, A., et al. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.062950 · Cited by 252
Sampath, S. C., Marazzi, I., Yap, K. L., Sampath, S. C., Krutchinsky, A. N., Mecklenbräuker, I., Viale, A. J., Rudensky, E., Zhou, M., Chait, B. T., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.06.026 · Cited by 249
Self-citationNiyonsaba, F., Ushio, H., Nagaoka, I., Okumura, K., & Ogawa, H. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.3.1776 · Cited by 248
Kondo, Y., Shen, L., Ahmed, S., Boumber, Y., Sekido, Y., Haddad, B. R., & Issa, J. J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002037 · Cited by 242
Mediator Links Epigenetic Silencing of Neuronal Gene Expression with X-Linked Mental Retardation
Ding, N., Zhou, H., Estève, P., Chin, H. G., Kim, S., Xu, X., Joseph, S., Friez, M. J., Schwartz, C. E., Pradhan, S., et al. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.05.023 · Cited by 238
Chen, H., Yan, Y., Davidson, T. L., Shinkai, Y., & Costa, M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0101 · Cited by 222
G9a Histone Methyltransferase Contributes to Imprinting in the Mouse Placenta
Wagschal, A., Sutherland, H. G. E., Woodfine, K., Henckel, A., Chébli, K., Schulz, R., Oakey, R. J., Bickmore, W. A., & Feil, R. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01111-07 · Cited by 187
Laboratory Protocols for Conditional Gene Targeting
Torres, R. M., & Kühn, R. (1997) · doi:10.1093/oso/9780199636778.001.0001 · Cited by 170
Afamin is a new member of the albumin, alpha-fetoprotein, and vitamin D-binding protein gene family.
Lichenstein, H. S., Lyons, D. E., Wurfel, M. M., Johnson, D. A., McGinley, M. D., Leidli, J. C., Trollinger, D. B., Mayer, J. P., Wright, S. D., & Zukowski, M. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32429-8 · Cited by 156
Laminin isoforms in development and disease
Schéele, S., Nyström, A., Durbeej, M., Talts, J. F., Ekblom, M., & Ekblom, P. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0182-5 · Cited by 155
Biological functions of maspin
Bailey, C. M., Khalkhali‐Ellis, Z., Seftor, E. A., & Hendrix, M. J. C. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20782 · Cited by 147
Estrogen action: A historic perspective on the implications of considering alternative approaches
Jensen, E. V., Jacobson, H. I., Walf, A. A., & Frye, C. A. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.08.013 · Cited by 133
Oien, K. A., McGregor, F., Butler, S., Ferrier, R. K., Downie, I., Bryce, S. D., Burns, S., & Keith, W. N. (2004) · The Journal of Pathology · doi:10.1002/path.1583 · Cited by 102
Genetic and epigenetic defects in mental retardation
Kramer, J. M., & van Bokhoven, H. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.08.009 · Cited by 91
A Jumonji (Jarid2) Protein Complex Represses cyclin D1 Expression by Methylation of Histone H3-K9
Shirato, H., Ogawa, S., Nakajima, K., Inagawa, M., Kojima, M., Tachibana, M., Shinkai, Y., & Takeuchi, T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804994200 · Cited by 86
Goldstone, A. P., & Beales, P. L. (2008) · Frontiers of hormone research · doi:10.1159/000115336 · Cited by 82
Cryptic terminal deletion of chromosome 9q34: a novel cause of syndromic obesity in childhood?
Cormier‐Daire, V., Molinari, F., Rio, M., Raoul, O., de Blois, M.-C., Romana, S. P., Vekemans, M. J. J., Münnich, A., & Colleaux, L. (2003) · Journal of Medical Genetics · doi:10.1136/jmg.40.4.300 · Cited by 68
Functional Analysis of Histone Methyltransferase G9a in B and T Lymphocytes
Thomas, L. R., Miyashita, H., Cobb, R. M., Pierce, S. E., Tachibana, M., Hobeika, E., Reth, M. G., Shinkai, Y., & Oltz, E. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.1.485 · Cited by 66
Nguyen, T. T. T., Cho, K., Stratton, S. A., & Barton, M. C. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.6.2147-2157.2005 · Cited by 60
Benarafa, C., Cooley, J., Zeng, W., Bird, P. I., & Remold‐O’Donnell, E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207080200 · Cited by 55
Characterization of mouse Dach2 , a homologue of Drosophila dachshund
Davis, R. J., Shen, W., Sandler, Y. I., Heanue, T. A., & Mardon, G. (2001) · Mechanisms of Development · doi:10.1016/s0925-4773(01)00307-0 · Cited by 53
Mammalian carboxylesterase 5: Comparative biochemistry and genomics
Holmes, R. S., Cox, L. A., & VandeBerg, J. L. (2008) · Comparative Biochemistry and Physiology Part D Genomics and Proteomics · doi:10.1016/j.cbd.2008.05.002 · Cited by 34
Behavioral phenotype in the 9q subtelomeric deletion syndrome: A report about two adult patients
Verhoeven, W. M. A., Kleefstra, T., & Egger, J. I. M. (2009) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31015 · Cited by 33
Generation of a conditional allele of the CBP gene in mouse
Zhang, Z., Hofmann, C., Casanova, E., Schütz, G., & Lutz, B. (2004) · genesis · doi:10.1002/gene.20068 · Cited by 27
Flagged first, then by citations
Cited by
Sorted by citations
Epigenetic protein families: a new frontier for drug discovery
Arrowsmith, C. H., Bountra, C., Fish, P. V., Lee, K., & Schapira, M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3674 · Cited by 1,327
Writing, erasing and reading histone lysine methylations
Hyun, K., Jeon, J., Park, K., & Kim, J. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.11 · Cited by 1,250
H3K9 methyltransferase G9a and the related molecule GLPPreprint
Shinkai, Y., & Tachibana, M. (2011) · Genes & Development · doi:10.1101/gad.2027411 · Cited by 571
A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells
Vedadi, M., Baršytė-Lovejoy, D., Liu, F., Rival‐Gervier, S., Allali‐Hassani, A., Labrie, V., Wigle, T. J., DiMaggio, P. A., Wasney, G. A., Siarheyeva, A., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.599 · Cited by 547
Padeken, J., Methot, S. P., & Gasser, S. M. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00483-w · Cited by 532
Metadata
- Authors
- Schaefer, A., Sampath, S. C., Intrator, A., Min, A., Gertler, T. S., Surmeier, D. J., Tarakhovsky, A., & Greengard, P.
- Affiliations
- Rockefeller University (US)
- Northwestern University (US)
- Corresponding author
- Tarakhovsky, Alexander
- Greengard, Paul
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 64
- Issue
- 5
- Pages
- 678-691
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2814156
- OpenAlex
- W2065364505
- Cited by
- 317
- References
- 57
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 14 · 2023: 11 · 2022: 12 · 2021: 17 · 2020: 16 · 2019: 20 · 2018: 16 · 2017: 24 · 2016: 23 · 2015: 27 · 2014: 28 · 2013: 24 · 2012: 24
- FWCI
- 9.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG09464, P01AG009464)
- National Institute of Mental Health (MH-074866, F30MH082522, MH082522, P50MH074866)
- National Institute on Drug Abuse (R03DA025962, DA025962)
- National Institute of General Medical Sciences (GM 07739, R01GM112811, T32GM007739)
- National Institute of Allergy and Infectious Diseases (AI068058, R01AI068058)
- National Institute of Neurological Disorders and Stroke (P01NS013742)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- EHMT1, histone methyltransferase, epigenetic regulation, cognition, learning and memory, motivation, environmental adaptation, adult neurons
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, Adaptation, Physiological, Central Nervous System Stimulants, Animals, Animals, Newborn, Behavior, Animal, Benzazepines, Body Weight, Caffeine, Cognition, Cognition Disorders, Conditioning, Classical, Exploratory Behavior, Fear, Food Preferences, Mice, Inbred DBA, Mice, Transgenic, Motor Activity, Histone-Lysine N-Methyltransferase, Mutagenesis, Dopamine Agonists, Maze Learning, Epigenesis, Genetic, Green Fluorescent Proteins, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Polycomb Repressive Complex 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
