Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia
Abstract
Chromatin remodeling may play a role in the neurobiology of schizophrenia and the process, therefore, may be considered as a therapeutic target. The SMARCA2 gene encodes BRM in the SWI/SNF chromatin-remodeling complex, and associations of single nucleotide polymorphisms (SNPs) to schizophrenia were found in two linkage disequilibrium blocks in the SMARCA2 gene after screening of 11 883 SNPs (rs2296212; overall allelic P = 5.8 x 10(-5)) and subsequent screening of 22 genes involved in chromatin remodeling (rs3793490; overall allelic P = 2.0 x 10(-6)) in a Japanese population. A risk allele of a missense polymorphism (rs2296212) induced a lower nuclear localization efficiency of BRM, and risk alleles of intronic polymorphisms (rs3763627 and rs3793490) were associated with low SMARCA2 expression levels in the postmortem prefrontal cortex. A significant correlation in the fold changes of gene expression from schizophrenic prefrontal cortex (from the Stanley Medical Research Institute online genomics database) was seen with suppression of SMARCA2 in transfected human cells by specific siRNA, and of orthologous genes in the prefrontal cortex of Smarca2 knockout mice. Smarca2 knockout mice showed impaired social interaction and prepulse inhibition. Psychotogenic drugs lowered Smarca2 expression while antipsychotic drugs increased it in the mouse brain. These findings support the existence of a role for BRM in the pathophysiology of schizophrenia.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
SMARCA2 is a member of the BAF-complex strongly implicated in several neurodevelopmental disorders including autism spectrum disorder.
“SMARCA2, a member of the BAF-complex strongly implicated in several neurodevelopmental disorders including ASD (79)”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [79]
Cites
Epigenetic programming by maternal behavior
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., & Meaney, M. J. (2004) · Nature Neuroscience · doi:10.1038/nn1276 · Cited by 6,177 · see citing works
Genomic Control for Association Studies
Devlin, B., & Roeder, K. (1999) · Biometrics · doi:10.1111/j.0006-341x.1999.00997.x · Cited by 3,162 · see citing works
Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., et al. (2008) · Science · doi:10.1126/science.1155174 · Cited by 1,800 · see citing works
Epigenetic regulation in psychiatric disorders
Tsankova, N., Renthal, W., Kumar, A., & Nestler, E. J. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2132 · Cited by 1,400 · see citing works
Covalent Modification of DNA Regulates Memory Formation
Miller, C. A., & Sweatt, J. D. (2007) · Neuron · doi:10.1016/j.neuron.2007.02.022 · Cited by 1,180 · see citing works
Homer: a protein that selectively binds metabotropic glutamate receptors
Brakeman, P., Lanahan, A. A., O’Brien, R., Roche, K. W., Barnes, C. A., Huganir, R. L., & Worley, P. F. (1997) · Nature · doi:10.1038/386284a0 · Cited by 1,115 · see citing works
Identification of loci associated with schizophrenia by genome-wide association and follow-up
Molecular Genetics of Schizophrenia Collaboration, O'Donovan, M. C., Craddock, N., Norton, N., Williams, H., Peirce, T., Moskvina, V., Nikolov, I., Hamshere, M., Carroll, L., et al. (2008) · Nature Genetics · doi:10.1038/ng.201 · Cited by 1,070 · see citing works
Self-citationAllen, N. C., Bagade, S., McQueen, M. B., Ioannidis, J. P. A., Kavvoura, F. K., Khoury, M. J., Tanzi, R. E., & Bertram, L. (2008) · Nature Genetics · doi:10.1038/ng.171 · Cited by 1,054 · see citing works
Tamkun, J. W., Deuring, R., Scott, M. P., Kissinger, M., Pattatucci, A. M. L., Kaufman, T. C., & Kennison, J. A. (1992) · Cell · doi:10.1016/0092-8674(92)90191-e · Cited by 966 · see citing works
Rb Interacts with Histone Deacetylase to Repress Transcription
Luo, R. X., Postigo, A. A., & Dean, D. C. (1998) · Cell · doi:10.1016/s0092-8674(00)80940-x · Cited by 957 · see citing works
What's Up and Down with Histone Deacetylation and Transcription?
Pazin, M. J., & Kadonaga, J. T. (1997) · Cell · doi:10.1016/s0092-8674(00)80211-1 · Cited by 820 · see citing works
Diversity and specialization of mammalian SWI/SNF complexes.Preprint
Wang, W., Xue, Y., Zhou, S., Kuo, A. C., Cairns, B. R., & Crabtree, G. R. (1996) · Genes & Development · doi:10.1101/gad.10.17.2117 · Cited by 707 · see citing works
Khavari, P. A., Peterson, C. L., Tamkun, J. W., Mendel, D. B., & Crabtree, G. R. (1993) · Nature · doi:10.1038/366170a0 · Cited by 670 · see citing works
Role of neurotrophic factors in depression
CASTREN, E., VOIKAR, V, & RANTAMAKI, T. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2006.08.009 · Cited by 667 · see citing works
Peterson, C. L., & Herskowitz, I. (1992) · Cell · doi:10.1016/0092-8674(92)90192-f · Cited by 601 · see citing works
Muchardt, C., & Yaniv, M. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06112.x · Cited by 588 · see citing works
Self-citationKadonaga, J. T. (1998) · Cell · doi:10.1016/s0092-8674(00)80924-1 · Cited by 554 · see citing works
Bredy, T. W., Wu, H., Crego, C., Zellhoefer, J., Sun, Y. E., & Barad, M. (2007) · Learning & Memory · doi:10.1101/lm.500907 · Cited by 548 · see citing works
Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure.Preprint
Hirschhorn, J. N., Brown, S. A., Clark, C. D., & Winston, F. (1992) · Genes & Development · doi:10.1101/gad.6.12a.2288 · Cited by 528 · see citing works
Genomic Control, a New Approach to Genetic-Based Association Studies
Devlin, B., Roeder, K., & Wasserman, L. (2001) · Theoretical Population Biology · doi:10.1006/tpbi.2001.1542 · Cited by 511 · see citing works
Repression and activation by multiprotein complexes that alter chromatin structure.Preprint
Kingston, R. E., Bunker, C. A., & Imbalzano, A. N. (1996) · Genes & Development · doi:10.1101/gad.10.8.905 · Cited by 444 · see citing works
Promoter targeting and chromatin remodeling by the SWI/SNF complex
Peterson, C. L., & Workman, J. L. (2000) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00068-x · Cited by 438 · see citing works
Altered control of cellular proliferation in the absence of mammalian brahma (SNF2α)
Reyes, J. C., Barra, J., Muchardt, C., Camus, A., Babinet, C., & Yaniv, M. (1998) · The EMBO Journal · doi:10.1093/emboj/17.23.6979 · Cited by 433 · see citing works
Self-citationGRR: graphical representation of relationship errors
Abecasis, G. R., Cherny, S. S., Cookson, W., & Cardon, L. R. (2001) · Bioinformatics · doi:10.1093/bioinformatics/17.8.742 · Cited by 383 · see citing works
Reisman, D., Sciarrotta, J., Wang, W., Funkhouser, W. K., & Weissman, B. E. (2003) · PubMed · Cited by 381 · see citing works
Genomewide association for schizophrenia in the CATIE study: results of stage 1
Sullivan, P. F., Lin, D. Y., Tzeng, J., van den Oord, E. J. C. G., Perkins, D. O., Stroup, T. S., Wagner, M. J., Lee, S., Wright, F. A., Zou, F., et al. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.25 · Cited by 354 · see citing works
Nagarajan, R., Hogart, A., Gwye, Y., Martin, M. R., & LaSalle, J. M. (2006) · Epigenetics · doi:10.4161/epi.1.4.3514 · Cited by 347 · see citing works
Chiba, H., Muramatsu, M., Nomoto, A., & Kato, H. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.10.1815 · Cited by 345 · see citing works
SWI2/SNF2 and Related Proteins: ATP-Driven Motors That Disrupt-Protein–DNA Interactions?
Pazin, M. J., & Kadonaga, J. T. (1997) · Cell · doi:10.1016/s0092-8674(00)81918-2 · Cited by 307 · 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
Human SWI/SNF Interconverts a Nucleosome between Its Base State and a Stable Remodeled State
Schnitzler, G. R., Sif, S., & Kingston, R. E. (1998) · Cell · doi:10.1016/s0092-8674(00)81217-9 · Cited by 282 · see citing works
Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia
Lencz, T., Morgan, T., Athanasiou, M., Dain, B., Reed, C. R., Kane, J. M., Kucherlapati, R., & Malhotra, A. K. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001983 · Cited by 278 · see citing works
The SNF/SWI family of global transcriptional activators
Carlson, M., & Laurent, B. C. (1994) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(94)90032-9 · Cited by 267 · see citing works
Risk of Malignancy in Patients With Schizophrenia or Bipolar Disorder: Nested Case-Control Study
Hippisley-Cox, J., Vinogradova, Y., Coupland, C., & Parker, C. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.12.1368 · Cited by 214 · see citing works
Cancer incidence in patients with schizophrenia and their first‐degree relatives – a meta‐analysis
Catts, V. S., Catts, S. V., O’Toole, B. I., & Frost, A. D. J. (2008) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2008.01163.x · Cited by 209 · see citing works
Szumlinski, K. K., Lominac, K. D., Kleschen, M. J., Oleson, E. B., Dehoff, M. H., Schwartz, M. K., Seeberg, P. H., Worley, P. F., & Kalivas, P. W. (2005) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2005.00120.x · Cited by 181 · see citing works
Fuchikami, M., Morinobu, S., Kurata, A., Yamamoto, S., & Yamawaki, S. (2008) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145708008997 · Cited by 178 · see citing works
A genome-wide association study in 574 schizophrenia trios using DNA pooling
Kirov, G., Zaharieva, I. T., Georgieva, L., Moskvina, V., Nikolov, I., Cichon, S., Hillmer, A. M., Toncheva, D. I., Owen, M. J., & O’Donovan, M. C. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.33 · Cited by 161 · see citing works
Li, J., Guo, Y., Schroeder, F. A., Youngs, R. M., Schmidt, T. W., Ferris, C. F., Konradi, C. L., & Akbarian, S. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02569.x · Cited by 151 · see citing works
Akbarian, S., Ruehl, M. G., Bliven, E. E., Luiz, L. A., Peranelli, A. C., Baker, S. P., Roberts, R. C., Bunney, W. E., Conley, R. C., Jones, E. G., et al. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.8.829 · Cited by 140 · see citing works
Schroeder, F. A., Penta, K. L., Matevossian, A., Jones, S. R., Konradi, C., Tapper, A. R., & Akbarian, S. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.15 · Cited by 139 · see citing works
Sun, A., Tawfik, O. W., Gayed, B. A., Thrasher, J. B., Hoestje, S. M., Li, C., & Li, B. (2006) · The Prostate · doi:10.1002/pros.20521 · Cited by 133 · see citing works
Genomic imprinting and the social brain
Isles, A. R., Davies, W., & Wilkinson, L. S. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.1942 · Cited by 119 · see citing works
Distinct Roles for Different Homer1 Isoforms in Behaviors and Associated Prefrontal Cortex Function
Lominac, K. D., Oleson, E. B., Pava, M. J., Klugmann, M., Schwarz, M. K., Seeburg, P. H., During, M. J., Worley, P. F., Kalivas, P. W., & Szumlinski, K. K. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3764-05.2005 · Cited by 118 · see citing works
An online database for brain disease research
Higgs, B. W., Elashoff, M. R., Richman, S., & Barci, B. M. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-70 · Cited by 113 · see citing works
Yamamichi, N., Inada, K.-I., Ichinose, M., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2601 · Cited by 100 · see citing works
Functional analysis of mouse Polycomb group genes.
van Lohuizen, M. (1998) · Cellular and Molecular Life Sciences (CMLS) · doi:10.1007/s000180050126 · Cited by 79 · see citing works
Methamphetamine alters expression of DNA methyltransferase 1 mRNA in rat brain
Numachi, Y., Shen, H., Yoshida, S., et al. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2006.12.052 · Cited by 74 · see citing works
Activators and repressors: making use of chromatin to regulate transcription
Wolffe, A. P., Wong, J., & Pruss, D. (1997) · Genes to Cells · doi:10.1046/j.1365-2443.1997.1260323.x · Cited by 74 · see citing works
Psychostimulant Alters Expression of DNA Methyltransferase mRNA in the Rat Brain
Numachi, Y., Yoshida, S., Yamashita, M., et al. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1316.013 · Cited by 54 · see citing works
Expression of Chromatin Remodeling Factors during Neural Differentiation
Machida, Y., Murai, K., Miyake, K., et al. (2001) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a002834 · Cited by 48 · see citing works
Prostate cancer and schizophrenia
Torrey, E. F. (2006) · Urology · doi:10.1016/j.urology.2006.08.1061 · Cited by 40 · see citing works
Histone modifications in status epilepticus induced by kainate.
Taniura, H., Sng, J., & Yoneda, Y. (2006) · PubMed · doi:10.14670/hh-21.785 · Cited by 34 · see citing works
Protein complexes for remodeling chromatin
Burns, L. G., & Peterson, C. L. (1997) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(96)00162-5 · Cited by 34 · see citing works
Supportive Evidence for Reduced Expression of GNB1L in Schizophrenia
Ishiguro, H., Koga, M., Horiuchi, Y., et al. (2008) · Schizophrenia Bulletin · doi:10.1093/schbul/sbn160 · Cited by 31 · see citing works
Self-citationA Histone Deacetylase Regulates Addiction
Impey, S. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.029 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder
Gandal, M. J., Zhang, P., Hadjimichael, E., Walker, R. L., Chen, C., Liu, S., Won, H., van Bakel, H., Varghese, M., Wang, Y., et al. (2018) · Science · doi:10.1126/science.aat8127 · Cited by 1,247 · see citing works
From neural development to cognition: unexpected roles for chromatin
Ronan, J. L., Wu, W., & Crabtree, G. R. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3413 · Cited by 544 · see citing works
An epigenetic framework for neurodevelopmental disorders: From pathogenesis to potential therapy
Millan, M. J. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.11.015 · Cited by 229 · see citing works
Place your BETs: the therapeutic potential of bromodomains
Prinjha, R. K., Witherington, J., & Lee, K. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.12.002 · Cited by 197 · see citing works
Zhang, Z., Cao, M., Chang, C.-W., Wang, C., Shi, X., Zhan, X., Birnbaum, S. G., Bezprozvanny, I., Huber, K. M., & Wu, J. I. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.00534-15 · Cited by 48 · see citing works
Zayed, A., Baranowski, C., Compagnion, A.-C., Vernochet, C., Karaki, S., Cuttoli, R. D.-D., Saint-Jour, E., Bhattacharya, S., Marti, F., Vanhoutte, P., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29380-8 · Cited by 17 · see citing works
Self-citation
- Authors
- Koga, M., Ishiguro, H., Yazaki, S., Horiuchi, Y., Arai, M., Niizato, K., Iritani, S., Itokawa, M., Inada, T., Iwata, N., Ozaki, N., Ujike, H., Kunugi, H., Sasaki, T., Takahashi, M., Watanabe, Y., Someya, T., Kakita, A., Takahashi, H., Nawa, H., Muchardt, C., Yaniv, M., & Arinami, T.
- Affiliations
- University of Tsukuba (JP)
- Tokyo Institute of Psychiatry (JP)
- Tokyo Metropolitan Matsuzawa Hospital (JP)
- Japan Science and Technology Agency (JP)
- Seiwa Hospital (JP)
- Fujita Health University (JP)
- Nagoya University (JP)
- Okayama University (JP)
- National Center of Neurology and Psychiatry (JP)
- The University of Tokyo (JP)
- Niigata University (JP)
- Brain Research Institute, Niigata University (JP)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Arinami, Tadao
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-04-10
- Volume
- 18
- Issue
- 13
- Pages
- 2483-2494
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2170353505
- Cited by
- 112
- References
- 56
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 10 · 2019: 12 · 2018: 7 · 2017: 7 · 2016: 1 · 2015: 7 · 2014: 8 · 2013: 10 · 2012: 10
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institute on Alcohol Abuse and Alcoholism
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- SMARCA2, BRM, SWI/SNF complex, schizophrenia, single nucleotide polymorphisms, genetic association, prefrontal cortex gene expression, nuclear localization, prepulse inhibition, social interaction, antipsychotic drugs, risk alleles
- MeSH terms
- Adult, Aged, Amino Acid Sequence, Animals, Cell Line, Cell Nucleus, DNA-Binding Proteins, Female, Humans, Interpersonal Relations, Male, Mice, Inbred C57BL, Middle Aged, Molecular Sequence Data, Psychotropic Drugs, Schizophrenia, Transcription Factors, Cohort Studies, Gene Expression, Case-Control Studies, Sequence Alignment, Prefrontal Cortex, Mice, Knockout, Polymorphism, Single Nucleotide, Protein Transport, Chromatin Assembly and Disassembly, Asian People, Mice
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