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Introducing ADNP and SIRT1 as new partners regulating microtubules and histone methylation

Molecular Psychiatry volume 26, pages 6550–6561 (2021)Cite this article

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Abstract

Activity-dependent neuroprotective protein (ADNP) is essential for brain formation and function. As such, de novo mutations in ADNP lead to the autistic ADNP syndrome and somatic ADNP mutations may drive Alzheimer’s disease (AD) tauopathy. Sirtuin 1 (SIRT1) is positively associated with aging, the major risk for AD. Here, we revealed two key interaction sites for ADNP and SIRT1. One, at the microtubule end-binding protein (EB1 and EB3) Tau level, with EB1/EB3 serving as amplifiers for microtubule dynamics, synapse formation, axonal transport, and protection against tauopathy. Two, on the DNA/chromatin site, with yin yang 1, histone deacetylase 2, and ADNP, sharing a DNA binding motif and regulating SIRT1, ADNP, and EB1 (MAPRE1). This interaction was linked to sex- and age-dependent altered histone modification, associated with ADNP/SIRT1/WD repeat-containing protein 5, which mediates the assembly of histone modification complexes. Single-cell RNA and protein expression analyses as well as gene expression correlations placed SIRT1–ADNP and either MAPRE1 (EB1), MAPRE3 (EB3), or both in the same mouse and human cell; however, while MAPRE1 seemed to be similarly regulated to ADNP and SIRT1, MAPRE3 seemed to deviate. Finally, we demonstrated an extremely tight correlation for the gene transcripts described above, including related gene products. This correlation was specifically abolished in affected postmortem AD and Parkinson’s disease brain select areas compared to matched controls, while being maintained in blood samples. Thus, we identified an ADNP–SIRT1 complex that may serve as a new target for the understanding of brain degeneration.

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Fig. 1: ADNP interacts with SIRT1.
Fig. 2: RNA-seq identification of ADNP–SIRT1 co-localization at the human single-cell level.
Fig. 3: ADNP and SIRT1 are co-regulated at the transcriptional level and both control specific histone H3 modifications.
Fig. 4: ADNP and SIRT1 correlate and interact with histone remodeling complex proteins.
Fig. 5: Marked dysregulation in AD postmortem brains, the ADNP/SIRT1 network.

References

  1. Pinhasov A, Mandel S, Torchinsky A, Giladi E, Pittel Z, Goldsweig AM, et al. Activity-dependent neuroprotective protein: a novel gene essential for brain formation. Brain Res Dev Brain Res. 2003;144:83–90.

    Article  CAS  PubMed  Google Scholar 

  2. Mandel S, Rechavi G, Gozes I. Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis. Dev Biol. 2007;303:814–24.

    Article  CAS  PubMed  Google Scholar 

  3. Bassan M, Zamostiano R, Davidson A, Pinhasov A, Giladi E, Perl O, et al. Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide. J Neurochem. 1999;72:1283–93.

    Article  CAS  PubMed  Google Scholar 

  4. Zamostiano R, Pinhasov A, Gelber E, Steingart RA, Seroussi E, Giladi E, et al. Cloning and characterization of the human activity-dependent neuroprotective protein. J Biol Chem. 2001;276:708–14.

    Article  CAS  PubMed  Google Scholar 

  5. Mandel S, Gozes I. Activity-dependent neuroprotective protein constitutes a novel element in the SWI/SNF chromatin remodeling complex. J Biol Chem. 2007;282:34448–56.

    Article  CAS  PubMed  Google Scholar 

  6. Mosch K, Franz H, Soeroes S, Singh PB, Fischle W. HP1 recruits activity-dependent neuroprotective protein to H3K9me3 marked pericentromeric heterochromatin for silencing of major satellite repeats. PloS One. 2011;6:e15894.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ostapcuk V, Mohn F, Carl SH, Basters A, Hess D, Iesmantavicius V, et al. Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes. Nature. 2018;557:739–43.

    Article  CAS  PubMed  Google Scholar 

  8. Sun X, Yu W, Li L, Sun Y. ADNP controls gene expression through local chromatin architecture by association with BRG1 and CHD4. Front Cell Dev Biol. 2020;8:553.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Mandel S, Spivak-Pohis I, Gozes I. ADNP differential nucleus/cytoplasm localization in neurons suggests multiple roles in neuronal differentiation and maintenance. J Mol Neurosci. 2008;35:127–41.

    Article  CAS  PubMed  Google Scholar 

  10. Oz S, Kapitansky O, Ivashco-Pachima Y, Malishkevich A, Giladi E, Skalka N, et al. The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins. Mol Psychiatry. 2014;19:1115–24.

    Article  CAS  PubMed  Google Scholar 

  11. Hacohen-Kleiman G, Sragovich S, Karmon G, Gao AYL, Grigg I, Pasmanik-Chor M, et al. Activity-dependent neuroprotective protein deficiency models synaptic and developmental phenotypes of autism-like syndrome. J Clin Investig. 2018;128:4956–69.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Amram N, Hacohen-Kleiman G, Sragovich S, Malishkevich A, Katz J, Touloumi O, et al. Sexual divergence in microtubule function: the novel intranasal microtubule targeting SKIP normalizes axonal transport and enhances memory. Mol Psychiatry. 2016;21:1467–76.

    Article  CAS  PubMed  Google Scholar 

  13. Ivashko-Pachima Y, Sayas CL, Malishkevich A, Gozes I. ADNP/NAP dramatically increase microtubule end-binding protein-Tau interaction: a novel avenue for protection against tauopathy. Mol Psychiatry. 2017;22:1335–44.

    Article  CAS  PubMed  Google Scholar 

  14. Grigg I, Ivashko-Pachima Y, Hait TA, Korenková V, Touloumi O, Lagoudaki R, et al. Tauopathy in the young autistic brain: novel biomarker and therapeutic target. Transl Psychiatry. 2020;10:228.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ivashko-Pachima Y, Hadar A, Grigg I, Korenková V, Kapitansky O, Karmon G, et al. Discovery of autism/intellectual disability somatic mutations in Alzheimer’s brains: mutated ADNP cytoskeletal impairments and repair as a case study. Mol Psychiatry. 2019.

  16. Vulih-Shultzman I, Pinhasov A, Mandel S, Grigoriadis N, Touloumi O, Pittel Z, et al. Activity-dependent neuroprotective protein snippet NAP reduces tau hyperphosphorylation and enhances learning in a novel transgenic mouse model. J Pharmacol Exp Therap. 2007;323:438–49.

    Article  CAS  Google Scholar 

  17. Banerjee B, Kestner CA, Stukenberg PT. EB1 enables spindle microtubules to regulate centromeric recruitment of Aurora B. J Cell Biol. 2014;204:947–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Van Dijck A, Vulto-van Silfhout AT, Cappuyns E, van der Werf IM, Mancini GM, Tzschach A. et al. Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP. Biol Psychiatry. 2019;85:287–97.

    Article  PubMed  Google Scholar 

  19. Helsmoortel C, Vulto-van Silfhout AT, Coe BP, Vandeweyer G, Rooms L, van den Ende J. et al. A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP. Nat Genet. 2014;46:380–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Braitch M, Kawabe K, Nyirenda M, Gilles LJ, Robins RA, Gran B, et al. Expression of activity-dependent neuroprotective protein in the immune system: possible functions and relevance to multiple sclerosis. Neuroimmunomodulation. 2010;17:120–5.

    Article  CAS  PubMed  Google Scholar 

  21. Malishkevich A, Marshall GA, Schultz AP, Sperling RA, Aharon-Peretz J, Gozes I. Blood-borne activity-dependent neuroprotective protein (ADNP) is correlated with premorbid intelligence, clinical stage, and Alzheimer’s disease biomarkers. J Alzheimer’s Dis. 2016;50:249–60.

    Article  CAS  Google Scholar 

  22. Hadar A, Milanesi E, Walczak M, Puzianowska-Kuznicka M, Kuznicki J, Squassina A, et al. SIRT1, miR-132 and miR-212 link human longevity to Alzheimer’s Disease. Sci Rep. 2018;8:8465.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Min SW, Cho SH, Zhou Y, Schroeder S, Haroutunian V, Seeley WW, et al. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron. 2010;67:953–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Min SW, Sohn PD, Cho SH, Swanson RA, Gan L. Sirtuins in neurodegenerative diseases: an update on potential mechanisms. Front Aging Neurosci. 2013;5:53.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Merenlender-Wagner A, Malishkevich A, Shemer Z, Udawela M, Gibbons A, Scarr E, et al. Autophagy has a key role in the pathophysiology of schizophrenia. Mol Psychiatry. 2015;20:126–32.

    Article  CAS  PubMed  Google Scholar 

  26. Esteves AR, Gozes I, Cardoso SM. The rescue of microtubule-dependent traffic recovers mitochondrial function in Parkinson’s disease. Biochim Biophys Acta. 2014;1842:7–21.

    Article  CAS  PubMed  Google Scholar 

  27. Yanagisawa S, Baker JR, Vuppusetty C, Koga T, Colley T, Fenwick P, et al. The dynamic shuttling of SIRT1 between cytoplasm and nuclei in bronchial epithelial cells by single and repeated cigarette smoke exposure. PloS One. 2018;13:e0193921.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Huang R, Xu Y, Wan W, Shou X, Qian J, You Z, et al. Deacetylation of nuclear LC3 drives autophagy initiation under starvation. Mol Cell. 2015;57:456–66.

    Article  CAS  PubMed  Google Scholar 

  29. Kuno A, Horio Y. SIRT1: a novel target for the treatment of muscular dystrophies. Oxid Med Cell Longev. 2016;2016:6714686.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Chen Y, Zhang H, Xu Z, Tang H, Geng A, Cai B, et al. A PARP1-BRG1-SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites. Nucleic Acids Res. 2019;47:8563–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang G, Fu Y, Hu F, Lan J, Xu F, Yang X, et al. Loss of BRG1 induces CRC cell senescence by regulating p53/p21 pathway. Cell Death Dis. 2017;8:e2607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Xu RY, Xu XW, Deng YZ, Ma ZX, Li XR, Zhao L, et al. Resveratrol attenuates myocardial hypoxia/reoxygenation-induced cell apoptosis through DJ-1-mediated SIRT1-p53 pathway. Biochem Biophys Res Commun. 2019;514:401–6.

    Article  CAS  PubMed  Google Scholar 

  33. Eubanks CG, Dayebgadoh G, Liu X, Washburn MP. Unravelling the biology of chromatin in health and cancer using proteomic approaches. Expert Rev Proteom. 2017;14:905–15.

    Article  CAS  Google Scholar 

  34. Wu S, Ge Y, Huang L, Liu H, Xue Y, Zhao Y. BRG1, the ATPase subunit of SWI/SNF chromatin remodeling complex, interacts with HDAC2 to modulate telomerase expression in human cancer cells. Cell Cycle. 2014;13:2869–78.

  35. Du L, Qian X, Li Y, Li XZ, He LL, Xu L, et al. Sirt1 inhibits renal tubular cell epithelial-mesenchymal transition through YY1 deacetylation in diabetic nephropathy. Acta Pharmacol Sin. 2020;42:242–51.

  36. Yao YL, Yang WM, Seto E. Regulation of transcription factor YY1 by acetylation and deacetylation. Mol Cell Biol. 2001;21:5979–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Vatine GD, Al-Ahmad A, Barriga BK, Svendsen S, Salim A, Garcia L, et al. Modeling psychomotor retardation using iPSCs from MCT8-deficient patients indicates a prominent role for the blood-brain barrier. Cell Stem Cell. 2017;20:831–43.e835.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Davenport AM, Huber FM, Hoelz A. Structural and functional analysis of human SIRT1. J Mol Biol. 2014;426:526–41.

    Article  CAS  PubMed  Google Scholar 

  39. Bjelic S, De Groot CO, Scharer MA, Jaussi R, Bargsten K, Salzmann M, et al. Interaction of mammalian end binding proteins with CAP-Gly domains of CLIP-170 and p150(glued). J Struct Biol. 2012;177:160–7.

    Article  CAS  PubMed  Google Scholar 

  40. Honnappa S, Gouveia SM, Weisbrich A, Damberger FF, Bhavesh NS, Jawhari H, et al. An EB1-binding motif acts as a microtubule tip localization signal. Cell. 2009;138:366–76.

    Article  CAS  PubMed  Google Scholar 

  41. Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ. PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Res. 2005;33:W363–7. Web Server issue

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mashiach E, Schneidman-Duhovny D, Andrusier N, Nussinov R, Wolfson HJ. FireDock: a web server for fast interaction refinement in molecular docking. Nucleic Acids Res. 2008;36:W229–32. Web Server issue

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Andrusier N, Nussinov R, Wolfson HJ. FireDock: fast interaction refinement in molecular docking. Proteins. 2007;69:139–59.

    Article  CAS  PubMed  Google Scholar 

  44. Wang C, Bradley P, Baker D. Protein-protein docking with backbone flexibility. J Mol Biol. 2007;373:503–19.

    Article  CAS  PubMed  Google Scholar 

  45. Nowakowski TJ, Bhaduri A, Pollen AA, Alvarado B, Mostajo-Radji MA, Di Lullo E, et al. Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex. Science. 2017;358:1318–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yan L, Yang M, Guo H, Yang L, Wu J, Li R, et al. Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells. Nat Struct Mol Biol. 2013;20:1131–9.

    Article  CAS  PubMed  Google Scholar 

  47. Papatheodorou I, Moreno P, Manning J, Fuentes AM-P, George N, Fexova S, et al. Expression Atlas update: from tissues to single cells. Nucleic Acids Res. 2019;48:D77–83.

    PubMed Central  Google Scholar 

  48. Battle A, Brown CD, Engelhardt BE, Montgomery SB. Genetic effects on gene expression across human tissues. Nature. 2017;550:204–13.

    Article  PubMed  Google Scholar 

  49. Malishkevich A, Amram N, Hacohen-Kleiman G, Magen I, Giladi E, Gozes I. Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer’s pathologies. Transl Psychiatry. 2015;5:e501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wang J, Zhuang J, Iyer S, Lin X-Y, Greven MC, Kim B-H, et al. Factorbook. org: a Wiki-based database for transcription factor-binding data generated by the ENCODE consortium. Nucleic Acids Res. 2012;41:D171–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Sunkin SM, Ng L, Lau C, Dolbeare T, Gilbert TL, Thompson CL, et al. Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system. Nucleic Acids Res. 2012;41:D996–1008.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Zheng R, Wan C, Mei S, Qin Q, Wu Q, Sun H, et al. Cistrome Data Browser: expanded datasets and new tools for gene regulatory analysis. Nucleic Acids Res. 2019;47:D729–35.

    Article  CAS  PubMed  Google Scholar 

  53. Li D, Hsu S, Purushotham D, Sears RL, Wang T. WashU epigenome browser update 2019. Nucleic Acids Res. 2019;47:W158–W65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Sood S, Gallagher IJ, Lunnon K, Rullman E, Keohane A, Crossland H, et al. A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status. Genome Biol. 2015;16:185.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Dinkel H, Van Roey K, Michael S, Kumar M, Uyar B, Altenberg B, et al. ELM 2016-data update and new functionality of the eukaryotic linear motif resource. Nucleic Acids Res. 2016;44:D294–300.

    Article  CAS  PubMed  Google Scholar 

  56. Patel A, Dharmarajan V, Vought VE, Cosgrove MS. On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex. J Biol Chem. 2009;284:24242–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Cai Y, Jin J, Swanson SK, Cole MD, Choi SH, Florens L, et al. Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex. J Biol Chem. 2010;285:4268–72.

    Article  CAS  PubMed  Google Scholar 

  58. Vaisburd S, Shemer Z, Yeheskel A, Giladi E, Gozes I. Risperidone and NAP protect cognition and normalize gene expression in a schizophrenia mouse model. Sci Rep. 2015;5:16300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Manosalva I, Gonzalez A. Aging changes the chromatin configuration and histone methylation of mouse oocytes at germinal vesicle stage. Theriogenology. 2010;74:1539–47.

    Article  CAS  PubMed  Google Scholar 

  60. Aboonq MS, Vasiliou SA, Haddley K, Quinn JP, Bubb VJ. Activity-dependent neuroprotective protein modulates its own gene expression. J Mol Neurosci. 2012;46:33–39.

    Article  CAS  PubMed  Google Scholar 

  61. Dai Y, Chen T, Ijaz H, Cho EH, Steinberg MH. SIRT1 activates the expression of fetal hemoglobin genes. Am J Hematol. 2017;92:1177–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gao J, Wang WY, Mao YW, Graff J, Guan JS, Pan L, et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature. 2010;466:1105–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Dresner E, Malishkevich A, Arviv C, Leibman Barak S, Alon S, Ofir R, et al. Novel evolutionary-conserved role for the activity-dependent neuroprotective protein (ADNP) family that is important for erythropoiesis. J Biol Chem. 2012;287:40173–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Liang WS, Dunckley T, Beach TG, Grover A, Mastroeni D, Walker DG, et al. Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain. Physiol Genomics. 2007;28:311–22.

    Article  CAS  PubMed  Google Scholar 

  65. Valdés Hernández MdC, Reid S, Mikhael S, Pernet C. Do 2-year changes in superior frontal gyrus and global brain atrophy affect cognition? Alzheimers Dement (Amst). 2018;10:706–16.

    Article  Google Scholar 

  66. Roth D, Fitton BP, Chmel NP, Wasiluk N, Straube A. Spatial positioning of EB family proteins at microtubule tips involves distinct nucleotide-dependent binding properties. J Cell Sci. 2018;132:jcs219550.

  67. Sayas CL, Medina M, Cuadros R, Ollá I, García E, Pérez M, et al. Role of tau N-terminal motif in the secretion of human tau by End Binding proteins. PloS One. 2019;14:e0210864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Sragovich S, Ziv Y, Vaisvaser S, Shomron N, Hendler T, Gozes I. The autism-mutated ADNP plays a key role in stress response. Transl Psychiatry. 2019;9:235.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Konar A, Rastogi M, Bhambri A. Brain region specific methylation and Sirt1 binding changes in MAOA promoter is associated with sexual dimorphism in early life stress induced aggressive behavior. Neurochemistry Int. 2019;129:104510.

    Article  CAS  Google Scholar 

  70. Abe M, Tsai SY, Jin S-G, Pfeifer GP, Szabó PE. Sex-specific dynamics of global chromatin changes in fetal mouse germ cells. PloS One. 2011;6:e23848.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Tatehana M, Kimura R, Mochizuki K, Inada H, Osumi N. Comprehensive histochemical profiles of histone modification in male germline cells during meiosis and spermiogenesis: Comparison of young and aged testes in mice. PloS One. 2020;15:e0230930.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mohapatra S, Chakraborty T, Shimizu S, Ohta K, Nagahama Y, Ohta K. Estrogen and estrogen receptors chauffeur the sex-biased autophagic action in liver. Cell Death Differ. 2020;27:3117–30.

  73. Ferrari R, de Llobet Cucalon LI, Di Vona C, Le Dilly F, Vidal E, Lioutas A, et al. TFIIIC binding to Alu elements controls gene expression via chromatin looping and histone acetylation. Mol Cell. 2020;77:475.e411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Breen MS, Garg P, Tang L, Mendonca D, Levy T, Barbosa M, et al. Episignatures stratifying Helsmoortel-Van Der Aa Syndrome show modest correlation with phenotype. Am J Hum Genet. 2020;107:555–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wang L, Shi FX, Li N, Cao Y, Lei Y, Wang JZ, et al. AMPK ameliorates tau acetylation and memory impairment through Sirt1. Mol Neurobiol. 2020;57:5011–25.

  76. Theendakara V, Peters-Libeu CA, Spilman P, Poksay KS, Bredesen DE, Rao RV. Direct transcriptional effects of apolipoprotein E. J Neurosci. 2016;36:685–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Szymanska M, Manthe S, Shrestha K, Girsh E, Harlev A, Kisliouk T, et al. Sirtuin-1 inhibits endothelin-2 expression in human granulosa-lutein cells via hypoxia inducible factor 1 alpha and epigenetic modifications. Biol Reprod. 2021;104:387–98.

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was partially supported by the following grants (IG): European Research Area Network (ERA-NET) Neuron ADNPinMED, the US–Israel Binational Science Foundation—US National Science Foundation (BSF-NSF 2016746), the Alberto Moscona Nisim (AMN) Foundation for the Advancement of Science, Art and Culture in Israel, as well as by Drs. Ronith and Armand Stemmer and Arthur Gerbi (French Friends of Tel Aviv University) and Anne and Alex Cohen (Canadian Friends of Tel Aviv University). OK and SS were supported by the Israeli BioInnovators Fellowship and Mentorship by Teva. SS is a former Levi Eshkol fellow supported by the Israel Ministry of Science and Technology, and a former awardee of the Tel Aviv University GRTF and The Naomi Foundation, as well as The Eldee Foundation/Bloomfield Family of Montreal awards for student exchange (Tel Aviv University/McGill University). YI-P was supported in part by the Aufzien Family Center for the Prevention and Treatment of Parkinson’s Disease (APPD) postdoctoral fellowship. This work is in partial fulfillment of OK and MG (PhD) and AL (MSc), respective thesis requirements at the Dr. Miriam and Sheldon G. Adelson Graduate School of Medicine, Sackler Faculty of Medicine, Tel Aviv University. We thank Gal Hacohen-Kleiman and Gidon Karmon for their help with Adnp+/– mouse colony as well as Prof. Rina Meidan and Jackson Sapuleni for the AB_2285964 SIRT1 validation antibodies.

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  1. These authors contributed equally: Adva Hadar, Oxana Kapitansky

Authors and Affiliations

  1. The Elton Laboratory for Neuroendocrinology, Sackler Faculty of Medicine, Sagol School of Neuroscience and Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv, Israel

    Adva Hadar, Oxana Kapitansky, Maram Ganaiem, Shlomo Sragovich, Alexandra Lobyntseva, Eliezer Giladi, Yanina Ivashko-Pachima & Illana Gozes

  2. Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Sagol School of Neuroscience and Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv, Israel

    Adva Hadar, Oxana Kapitansky, Maram Ganaiem, Shlomo Sragovich, Alexandra Lobyntseva, Eliezer Giladi, David Gurwitz, Yanina Ivashko-Pachima & Illana Gozes

  3. Weizmann Institute of Science, Rehovot, Israel

    Adva Hadar

  4. Bioinformatics Unit, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

    Adva Yeheskel

  5. The Department of Physiology and Cell Biology, Faculty of Health Sciences, The Regenerative Medicine and Stem Cell (RMSC) Research Center and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Aliza Avitan & Gad D. Vatine

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NAP (CP201) use is under patent protection (US patent nos. US7960334, US8618043, US10912819) and provisional patent applications, Ramot at Tel Aviv University.

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Hadar, A., Kapitansky, O., Ganaiem, M. et al. Introducing ADNP and SIRT1 as new partners regulating microtubules and histone methylation. Mol Psychiatry 26, 6550–6561 (2021). https://doi.org/10.1038/s41380-021-01143-9

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