Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis
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Complete deficiency in activity-dependent neuroprotective protein (ADNP) results in neural tube closure defects and death at days 8.5-9.5 of gestation in the mouse (E8.5-9.5). To elucidate ADNP associated pathways, Affymetrix 22,690-oligonucleotide-based microarrays were used on ADNP knockout and control mouse embryos (E9) separated completely from extra embryonic tissue. Marked differences in expression profiles between ADNP-deficient embryos and ADNP-expressing embryos were discovered. Specifically, a group of dramatically up-regulated gene transcripts in the ADNP-deficient embryos were clustered into a family encoding for proteins enriched in the visceral endoderm such as apolipoproteins, cathepsins and methallotionins. In contrast, a down regulated gene cluster associated with ADNP-deficiency in the developing embryo consisted of organogenesis markers including neurogenesis (Ngfr, neurogenin1, neurod1) and heart development (Myl2). The pluripotent P19 cells were used for ADNP-chromatin-immunoprecipitation, showing direct interactions with multiple relevant gene promoters including members of the up-regulated as well as the down-regulated gene clusters. A comparison between non-differentiated and neuro-differentiated P19 cells revealed increased chromatin interaction of ADNP with chromatin from differentiated cells. These results place ADNP at a crucial point of gene regulation, repressing potential endoderm genes and enhancing genes associated with organogenesis/neurogenesis.
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Among genes reported as differentially expressed in Adnp-/- and Adnp+/- mice, only PLAGL2 was differentially regulated in the patients.
“Of the other genes reported as differentially expressed in Adnp-/-23 and Adnp+/-18 mice (down: CCNC, TMPO, PLAGL2; up: ABCF3), only PLAGL2 was found to be differentially regulated in our patients (Supplementary Fig. 3e).”
From A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP (2014) · cites this paper as [23]
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Magen, I., & Gozes, I. (2013) · Neuropeptides · doi:10.1016/j.npep.2013.10.011 · Cited by 52 · see citing works
Self-citationEpigenetic regulation of autophagy-related genes: Implications for neurodevelopmental disorders
Lewerissa, E., Kasri, N. N., & Linda, K. (2023) · Autophagy · doi:10.1080/15548627.2023.2250217 · Cited by 53 · see citing works
The autism-mutated ADNP plays a key role in stress response
Sragovich, S., Ziv, Y., Vaisvaser, S., Shomron, N., Hendler, T., & Gozes, I. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0569-4 · Cited by 51 · see citing works
Self-citationGozes, I., Patterson, M. C., Dijck, A. V., Kooy, R. F., Peeden, J., Eichenberger, J. A., Zawacki-Downing, A., & Bedrosian‐Sermone, S. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00107 · Cited by 50 · see citing works
Self-citationDresner, E., Malishkevich, A., Arviv, C., Leibman Barak, S., Alon, S., Ofir, R., Gothilf, Y., & Gozes, I. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.387027 · Cited by 47 · see citing works
Self-citationD’Incal, C. P., Rossem, K. E. V., Man, K. D., Konings, A., Dijck, A. V., Rizzuti, L., Vitriolo, A., Testa, G., Gozes, I., Berghe, W. V., et al. (2023) · Clinical Epigenetics · doi:10.1186/s13148-023-01450-8 · Cited by 51 · see citing works
Self-citationZhang, Z., Zhang, Q., Xiao, Q., Sun, H., Gao, H., Yang, Y., Chen, J., Li, Z., Xue, M., Ma, P., et al. (2018) · Animal Genetics · doi:10.1111/age.12730 · Cited by 49 · see citing works
Resolving the Synaptic versus Developmental Dichotomy of Autism Risk Genes
Heavner, W. E., & Smith, S. E. P. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.01.009 · Cited by 48 · see citing works
Davunetide: Peptide Therapeutic in Neurological Disorders
Magen, I., & Gozes, I. (2014) · Current Medicinal Chemistry · doi:10.2174/0929867321666140217124945 · Cited by 45 · see citing works
Self-citationPescosolido, M. F., Schwede, M., Harrison, A. J., Schmidt, M., Uzun, E. D. G., Chen, W. S., Donahue, J. P., Shur, N. E., Jerskey, B. A., Phornphutkul, C., et al. (2014) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2014-102444 · Cited by 43 · see citing works
Bennison, S. A., Blazejewski, S. M., Liu, X., Hacohen-Kleiman, G., Sragovich, S., Zoidou, S., Touloumi, O., Grigoriadis, N., Gozes, I., & Toyo-oka, K. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01939-3 · Cited by 42 · see citing works
Self-citationMutations in ADNP affect expression and subcellular localization of the protein
Cappuyns, E., Huyghebaert, J., Vandeweyer, G., & Kooy, R. F. (2018) · Cell Cycle · doi:10.1080/15384101.2018.1471313 · Cited by 38 · see citing works
The Compassionate Side of Neuroscience: Tony Sermone’s Undiagnosed Genetic Journey—ADNP Mutation
Gozes, I., Helsmoortel, C., Vandeweyer, G., der Aa, N. V., Kooy, R. F., & Bedrosian‐Sermone, S. (2015) · Journal of Molecular Neuroscience · doi:10.1007/s12031-015-0586-6 · Cited by 41 · see citing works
Self-citationIvashko‐Pachima, Y., Maor-Nof, M., & Gozes, I. (2019) · PLoS ONE · doi:10.1371/journal.pone.0213666 · Cited by 40 · see citing works
Self-citationCritical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy
Gozes, I., Gold, Lorenzl, Stewart, A. J., Morimoto, B. H., & Williams (2012) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s12518 · Cited by 39 · see citing works
Self-citationKushnir, M., Dresner, E., Mandel, S., & Gozes, I. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05173.x · Cited by 38 · see citing works
Self-citationCho, H., Yoo, T., Moon, H., Kang, H., Yang, Y., Kang, M., Yang, E., Lee, D., Hwang, D., Kim, H., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02129-5 · Cited by 36 · see citing works
Analysis of the human HP1 interactome reveals novel binding partners
Rosnoblet, C., Vandamme, J., Völkel, P., & Angrand, P. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.08.059 · Cited by 37 · see citing works
Evidence of a Cardiovascular Function for Microtubule-Associated Protein Tau
Betrie, A. H., Ayton, S., Bush, A. I., Angus, J. A., Lei, P., & Wright, C. E. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161093 · Cited by 35 · see citing works
Ganaiem, M., Karmon, G., Ivashko‐Pachima, Y., & Gozes, I. (2022) · Cells · doi:10.3390/cells11192994 · Cited by 33 · see citing works
Self-citationGozes, I., Yeheskel, A., & Pasmanik‐Chor, M. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142490 · Cited by 33 · see citing works
Self-citationCosgrave, A. S., McKay, J. S., Bubb, V. J., Morris, R., Quinn, J. P., & Thippeswamy, T. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.02.005 · Cited by 33 · see citing works
Identification of New Tumor Suppressor Genes in Triple-Negative Breast Cancer
Rangel, R., Guzman‐Rojas, L., Kodama, T., Kodama, M., Newberg, J. Y., Copeland, N. G., & Jenkins, N. A. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0785 · Cited by 33 · see citing works
Yang, M., Chen, S.-C., Lin, Y., Lee, Y., Huang, M., Chen, K., Wu, H., Lin, P., Gozes, I., & Tyan, Y. (2019) · Journal of Food and Drug Analysis · doi:10.1016/j.jfda.2018.11.009 · Cited by 33 · see citing works
Self-citationGanaiem, M., Gildor, N. D., Shazman, S., Karmon, G., Ivashko‐Pachima, Y., & Gozes, I. (2023) · Cells · doi:10.3390/cells12182251 · Cited by 30 · see citing works
Self-citationGiladi, E., Hill, J. M., Dresner, E., Stack, C. M., & Gozes, I. (2007) · Journal of Molecular Neuroscience · doi:10.1007/s12031-007-9003-0 · Cited by 30 · see citing works
Self-citationBrown, B. P., Kang, S., Gawelek, K., Zacharias, R. A., Anderson, S. R., Turner, C. P., & Morris, J. K. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.12.076 · Cited by 29 · see citing works
Pleiotropy of autism-associated chromatin regulators
Lasser, M. C., Sun, N., Xu, Y., Wang, S., Drake, S., Law, K., Gonzalez, S., Wang, B., Drury, V., Castillo, O., et al. (2023) · Development · doi:10.1242/dev.201515 · Cited by 29 · see citing works
Baubet, V., Xiang, C., Molczan, A., Roccograndi, L., Melamed, S., & Dahmane, N. (2012) · Development · doi:10.1242/dev.075606 · Cited by 29 · see citing works
A convergent mechanism of high risk factors ADNP and POGZ in neurodevelopmental disorders
Conrow‐Graham, M., Williams, J. B., Martin, J. A., Zhong, P., Cao, Q., Rein, B. A., & Yan, Z. (2022) · Brain · doi:10.1093/brain/awac152 · Cited by 28 · see citing works
Gozes, I., Iram, T., Maryanovsky, E., Arviv, C., Rozenberg, L., Schirer, Y., Giladi, E., & Furman-Assaf, S. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131664 · Cited by 27 · see citing works
Self-citationFernández-Montesinos, R., Torres, M., Baglietto‐Vargas, D., Gutiérrez, A., Gozes, I., Vitórica, J., & Pozo, D. (2009) · Journal of Molecular Neuroscience · doi:10.1007/s12031-009-9300-x · Cited by 27 · see citing works
Self-citationIvashko‐Pachima, Y., & Gozes, I. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.07.008 · Cited by 25 · see citing works
Self-citationKaragoz, K., Mehta, G. A., Khella, C. A., Khanna, P., & Gatza, M. L. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.11.009 · Cited by 25 · see citing works
Developmental Phenotype of the Rare Case of DJ Caused by a Unique ADNP Gene De Novo Mutation
Levine, J., Cohen, D., Herman, C., Verloès, A., Guinchat, V., Diaz, L., Cravero, C., Mandel, A., & Gozes, I. (2019) · Journal of Molecular Neuroscience · doi:10.1007/s12031-019-01333-9 · Cited by 24 · see citing works
Self-citationTownsend, J. A., Braz, C. U., Taylor, T., & Khatib, H. (2022) · Current Zoology · doi:10.1093/eep/dvac029 · Cited by 24 · see citing works
Zemlyak, I., Manley, N. C., Vulih, I., Cutler, A. B., Graber, K., Sapolsky, R. M., & Gozes, I. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06415.x · Cited by 24 · see citing works
Self-citationFerreira, A. C. F., Szeto, A. C. H., Clark, P. A., Crisp, A., Kozik, P., Jolin, H. E., & McKenzie, A. N. J. (2023) · Immunity · doi:10.1016/j.immuni.2023.05.010 · Cited by 23 · see citing works
Levine, J., Hakim, F., Kooy, R. F., & Gozes, I. (2022) · Journal of Molecular Neuroscience · doi:10.1007/s12031-022-02048-0 · Cited by 23 · see citing works
Self-citationKolevzon, A. L., Levy, T., Barkley, S. B., Bedrosian‐Sermone, S., Davis, M. M., Foss‐Feig, J. H., Halpern, D. B., Keller, K., Kostić, A., Layton, C., et al. (2022) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2022.100138 · Cited by 23 · see citing works
Ziv, Y., Rahamim, N., Lezmy, N., Even‐Chen, O., Shaham, O., Malishkevich, A., Giladi, E., Elkon, R., Gozes, I., & Barak, S. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0132-7 · Cited by 22 · see citing works
Self-citationSingle Cell ADNP Predictive of Human Muscle Disorders: Mouse Knockdown Results in Muscle Wasting
Kapitansky, O., Karmon, G., Sragovich, S., Hadar, A., Shahoha, M., Jaljuli, I., Bikovski, L., Giladi, E., Pálovics, R., Iram, T., et al. (2020) · Cells · doi:10.3390/cells9102320 · Cited by 20 · see citing works
Self-citationGozes, I. (2010) · Peptides · doi:10.1016/j.peptides.2010.10.030 · Cited by 21 · see citing works
Self-citationDysregulated miRNAome and Proteome of PPRV Infected Goat PBMCs Reveal a Coordinated Immune Response
Khanduri, A., Sahu, A. R., Wani, S. A., Khan, R. I. N., Pandey, A., Saxena, S., Malla, W. A., Mondal, P., Rajak, K. K., Muthuchelvan, D., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02631 · Cited by 21 · see citing works
Shapira, G., Karmon, G., Hacohen-Kleiman, G., Ganaiem, M., Shazman, S., Theotokis, P., Grigoriadis, N., Shomron, N., & Gozes, I. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02879-w · Cited by 20 · see citing works
Self-citationGozes, I. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23808 · Cited by 20 · see citing works
Self-citationD’Incal, C. P., Dijck, A. V., Ibrahim, J., Man, K. D., Bastini, L., Konings, A., Elinck, E., Theys, C., Gozes, I., Marušić, Z., et al. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01743-w · Cited by 18 · see citing works
Self-citationGozes, I., & Ivashko‐Pachima, Y. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00205 · Cited by 18 · see citing works
Self-citationNeuroprotective Protein and Carboxypeptidase E
Koshimizu, H., Senatorov, V. V., Loh, Y. P., & Gozes, I. (2009) · Journal of Molecular Neuroscience · doi:10.1007/s12031-008-9164-5 · Cited by 18 · see citing works
Self-citationSomatic Mutations and Alzheimer’s Disease
Downey, J., Lam, J. C. K., Li, V. O. K., & Gozes, I. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220643 · Cited by 17 · see citing works
Self-citationD-SAL and NAP: Two Peptides Sharing a SIP Domain
Gozes, I., Sragovich, S., Schirer, Y., & Idan-Feldman, A. (2016) · Journal of Molecular Neuroscience · doi:10.1007/s12031-015-0701-8 · Cited by 17 · see citing works
Self-citationADNP Regulates Cognition: A Multitasking Protein
Gozes, I. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00873 · Cited by 16 · see citing works
Self-citationADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway
Zhu, S., Xu, Z., Zeng, Y., Long, Y., Fan, G., Ding, Q., Wen, Y., Cao, J., Dai, T., Han, W., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.491129 · Cited by 16 · see citing works
Genetics, Gene Expression and Bioinformatics of the Pituitary Gland
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Maugeri, G., D’Amico, A. G., Magrì, B., Giunta, S., Musumeci, G., Saccone, S., Federico, C., Scollo, D., Longo, A., Avitabile, T., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24086895 · Cited by 15 · see citing works
Davunetide improves spatial learning and memory in Alzheimer's disease-associated rats
Zhang, J., Wei, S.-Y., Yuan, L., Kong, L., Zhang, S., Wang, Z., Wu, M., & Qi, J. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.02.038 · Cited by 15 · see citing works
Kapitansky, O., & Gozes, I. (2019) · GeroScience · doi:10.1007/s11357-019-00079-x · Cited by 15 · see citing works
Self-citationMicrotubule-Tau Interaction as a Therapeutic Target for Alzheimer’s Disease
Ivashko‐Pachima, Y., Zhou, L.-Y., Lei, P., & Gozes, I. (2016) · Journal of Molecular Neuroscience · doi:10.1007/s12031-016-0715-x · Cited by 15 · see citing works
Self-citationCeramide synthases in mammalians, worms, and insects: emerging schemes
Voelzmann, A., & Bauer, R. (2010) · BioMolecular Concepts · doi:10.1515/bmc.2010.028 · Cited by 15 · see citing works
- Authors
- Mandel, S., Rechavi, G., & Gozes, I.
- Affiliations
- Tel Aviv University (IL)
- Corresponding author
- Gozes, Illana
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 303
- Issue
- 2
- Pages
- 814-824
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W2124865989
- Cited by
- 167
- References
- 47
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 14 · 2023: 11 · 2022: 10 · 2021: 3 · 2020: 12 · 2019: 10 · 2018: 11 · 2017: 12 · 2016: 9 · 2015: 9 · 2014: 11 · 2013: 4 · 2012: 6
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2366 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- ADNP, chromatin binding, gene expression regulation, organogenesis, neurogenesis, heart development, promoter binding, P19 cells, gene expression profiling
- MeSH terms
- Chromobox Protein Homolog 5, Animals, Base Sequence, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, Female, Models, Biological, Nerve Tissue Proteins, Pregnancy, DNA Primers, Mice, Knockout, Homeodomain Proteins, Gene Expression Regulation, Developmental, Gene Expression Profiling, Embryonic Development, Mice
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