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ETV5 is Essential for Neuronal Differentiation of Human Neural Progenitor Cells by Repressing NEUROG2 Expression

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Abstract

Neural progenitor cells (NPCs) are multipotent cells that have the potential to produce neurons and glial cells in the neural system. NPCs undergo identity maintenance or differentiation regulated by different kinds of transcription factors. Here we present evidence that ETV5, which is an ETS transcription factor, promotes the generation of glial cells and drives the neuronal subtype-specific genes in newly differentiated neurons from the human embryonic stem cells-derived NPCs. Next, we find a new role for ETV5 in the repression of NEUROG2 expression in NPCs. ETV5 represses NEUROG2 transcription via NEUROG2 promoter and requires the ETS domain. We identify ETV5 has the binding sites and is implicated in silent chromatin in NEUROG2 promoter by chromatin immunoprecipitation (ChIP) assays. Further, NEUROG2 transcription repression by ETV5 was shown to be dependent on a transcriptional corepressor (CoREST). During NPC differentiation toward neurons, ETV5 represses NEUROG2 expression and blocks the appearance of glutamatergic neurons. This finding suggests that ETV5 negatively regulates NEUROG2 expression and increases the number of GABAergic subtype neurons derived from NPCs. Thus, ETV5 represents a potent new candidate protein with benefits for the generation of GABAergic neurons.

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References

  1. Breunig, J. J., Haydar, T. F., & Rakic, P. (2011). Neural stem cells: Historical perspective and future prospects. Neuron, 70, 614–625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Haubensak, W., Attardo, A., Denk, W., & Huttner, W. B. (2004). Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: A major site of neurogenesis. Proceedings of the National Academy of Sciences of the United States of America, 101, 3196–3201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Morrison, S. J., & Kimble, J. (2006). Asymmetric and symmetric stem-cell divisions in development and cancer. Nature, 441, 1068–1074.

    Article  CAS  PubMed  Google Scholar 

  4. Fishell, G., & Kriegstein, A. R. (2003). Neurons from radial glia: The consequences of asymmetric inheritance. Current Opinion in Neurobiology, 13, 34–41.

    Article  CAS  PubMed  Google Scholar 

  5. Taverna, E., Gotz, M., & Huttner, W. B. (2014). The cell biology of neurogenesis: Toward an understanding of the development and evolution of the neocortex. Annual Review of Cell and Developmental Biology, 30, 465–502.

    Article  CAS  PubMed  Google Scholar 

  6. Miller, F. D., & Gauthier, A. S. (2007). Timing is everything: Making neurons versus glia in the developing cortex. Neuron, 54, 357–369.

    Article  CAS  PubMed  Google Scholar 

  7. Kriegstein, A., & Alvarez-Buylla, A. (2009). The glial nature of embryonic and adult neural stem cells. Annual Review of Neuroscience, 32, 149–184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tropepe, V., Sibilia, M., Ciruna, B. G., Rossant, J., Wagner, E. F., & van der Kooy, D. (1999). Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon. Developmental Biology, 208, 166–188.

    Article  CAS  PubMed  Google Scholar 

  9. Villa, A., Snyder, E. Y., Vescovi, A., & Martinez-Serrano, A. (2000). Establishment and properties of a growth factor-dependent, perpetual neural stem cell line from the human CNS. Experimental Neurology, 161, 67–84.

    Article  CAS  PubMed  Google Scholar 

  10. Menard, C., Hein, P., Paquin, A., Savelson, A., Yang, X. M., Lederfein, D., Barnabe-Heider, F., Mir, A. A., Sterneck, E., Peterson, A. C., Johnson, P. F., Vinson, C., & Miller, F. D. (2002). An essential role for a MEK-C/EBP pathway during growth factor-regulated cortical neurogenesis. Neuron, 36, 597–610.

    Article  CAS  PubMed  Google Scholar 

  11. Paquin, A., Hordo, C., Kaplan, D. R., & Miller, F. D. (2009). Costello syndrome H-Ras alleles regulate cortical development. Developmental Biology, 330, 440–451.

    Article  CAS  PubMed  Google Scholar 

  12. Li, X., Newbern, J. M., Wu, Y., Morgan-Smith, M., Zhong, J., Charron, J., & Snider, W. D. (2012). MEK is a key regulator of Gliogenesis in the developing brain. Neuron, 75, 1035–1050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hollenhorst, P. C., McIntosh, L. P., & Graves, B. J. (2011). Genomic and biochemical insights into the specificity of ETS transcription factors. Annual Review of Biochemistry, 80, 437–471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sharrocks, A. D. (2001). The ETS-domain transcription factor family. Nature Reviews. Molecular Cell Biology, 2, 827–837.

    Article  CAS  PubMed  Google Scholar 

  15. Kalkan, T., Bornelov, S., Mulas, C., Diamanti, E., Lohoff, T., Ralser, M., Middelkamp, S., Lombard, P., Nichols, J., & Smith, A. (2019). Complementary activity of ETV5, RBPJ, and TCF3 drives formative transition from naive pluripotency. Cell Stem Cell, 24, 785–801 e7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Akagi, T., Kuure, S., Uranishi, K., Koide, H., Costantini, F., & Yokota, T. (2015). ETS-related transcription factors ETV4 and ETV5 are involved in proliferation and induction of differentiation-associated genes in embryonic stem (ES) cells. The Journal of Biological Chemistry, 290, 22460–22473.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ahmad, S. T., Rogers, A. D., Chen, M. J., Dixit, R., Adnani, L., Frankiw, L. S., Lawn, S. O., Blough, M. D., M Alshehri, W. W., Marra, M. A., Robbins, S. M., Cairncross, J. G., Schuurmans, C., & Chan, J. A. (2019). Capicua regulates neural stem cell proliferation and lineage specification through control of Ets factors. Nature Communications, 10, 2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hagedorn, L., Paratore, C., Brugnoli, G., Baert, J. L., Mercader, N., Suter, U., & Sommer, L. (2000). The Ets domain transcription factor Erm distinguishes rat satellite glia from Schwann cells and is regulated in satellite cells by neuregulin signaling. Developmental Biology, 219, 44–58.

    Article  CAS  PubMed  Google Scholar 

  19. Fontanet, P., Irala, D., Alsina, F. C., Paratcha, G., & Ledda, F. (2013). Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde signaling and axonal growth of DRG sensory neurons in response to NGF. The Journal of Neuroscience, 33, 15940–15951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liu, D., Liu, Z., Liu, H., Li, H., Pan, X., & Li, Z. (2016). Brain-derived neurotrophic factor promotes vesicular glutamate transporter 3 expression and neurite outgrowth of dorsal root ganglion neurons through the activation of the transcription factors Etv4 and Etv5. Brain Research Bulletin, 121, 215–226.

    Article  CAS  PubMed  Google Scholar 

  21. Fontanet, P. A., Rios, A. S., Alsina, F. C., Paratcha, G., & Ledda, F. (2018). Pea3 transcription factors, Etv4 and Etv5, are required for proper hippocampal dendrite development and plasticity. Cerebral Cortex, 28, 236–249.

    Article  PubMed  Google Scholar 

  22. Bosco, A., Bureau, C., Affaticati, P., Gaspar, P., Bally-Cuif, L., & Lillesaar, C. (2013). Development of hypothalamic serotoninergic neurons requires Fgf signalling via the ETS-domain transcription factor Etv5b. Development, 140, 372–384.

    Article  CAS  PubMed  Google Scholar 

  23. Breunig, J. J., Levy, R., Antonuk, C. D., Molina, J., Dutra-Clarke, M., Park, H., Akhtar, A. A., Kim, G. B., Hu, X., Bannykh, S. I., Verhaak, R. G., & Danielpour, M. (2015). Ets factors regulate neural stem cell depletion and gliogenesis in Ras pathway Glioma. Cell Reports, 12, 258–271.

    Article  CAS  PubMed  Google Scholar 

  24. Newton, K., Dugger, D. L., Sengupta-Ghosh, A., Ferrando, R. E., Chu, F., Tao, J., Lam, W., Haller, S., Chan, S., Sa, S., Dunlap, D., Eastham-Anderson, J., Ngu, H., Hung, J., French, D. M., Webster, J. D., Bolon, B., Liu, J., Reja, R., Kummerfeld, S., Chen, Y. J., Modrusan, Z., Lewcock, J. W., & Dixit, V. M. (2018). Ubiquitin ligase COP1 coordinates transcriptional programs that control cell type specification in the developing mouse brain. Proceedings of the National Academy of Sciences of the United States of America, 115, 11244–11249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., & Jones, J. M. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.

    Article  CAS  PubMed  Google Scholar 

  26. Zhang, S. C., Wernig, M., Duncan, I. D., Brustle, O., & Thomson, J. A. (2001). In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nature Biotechnology, 19, 1129–1133.

    Article  CAS  PubMed  Google Scholar 

  27. Chi, L., Fan, B., Feng, D., Chen, Z., Liu, Z., Hui, Y., X, X., Ma, L., Fang, Y., Zhang, Q., Jin, G., Liu, L., Guan, F., & Zhang, X. (2017). The Dorsoventral patterning of human forebrain follows an activation/transformation model. Cerebral Cortex, 27, 2941–2954.

    PubMed  Google Scholar 

  28. Zecevic, N., Chen, Y., & Filipovic, R. (2005). Contributions of cortical subventricular zone to the development of the human cerebral cortex. The Journal of Comparative Neurology, 491, 109–122.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Bayatti, N., Moss, J. A., Sun, L., Ambrose, P., Ward, J. F., Lindsay, S., & Clowry, G. J. (2008). A molecular neuroanatomical study of the developing human neocortex from 8 to 17 postconceptional weeks revealing the early differentiation of the subplate and subventricular zone. Cerebral Cortex, 18, 1536–1548.

    Article  PubMed  Google Scholar 

  30. Delalle, I., Evers, P., Kostovic, I., & Uylings, H. B. (1997). Laminar distribution of neuropeptide Y-immunoreactive neurons in human prefrontal cortex during development. The Journal of Comparative Neurology, 379, 515–522.

    Article  CAS  PubMed  Google Scholar 

  31. Miller, J. A., Ding, S. L., Sunkin, S. M., Smith, K. A., Ng, L., Szafer, A., Ebbert, A., Riley, Z. L., Royall, J. J., Aiona, K., Arnold, J. M., Bennet, C., Bertagnolli, D., Brouner, K., Butler, S., Caldejon, S., Carey, A., Cuhaciyan, C., Dalley, R. A., Dee, N., Dolbeare, T. A., Facer, B. A., Feng, D., Fliss, T. P., Gee, G., Goldy, J., Gourley, L., Gregor, B. W., Gu, G., Howard, R. E., Jochim, J. M., Kuan, C. L., Lau, C., Lee, C. K., Lee, F., Lemon, T. A., Lesnar, P., McMurray, B., Mastan, N., Mosqueda, N., Naluai-Cecchini, T., Ngo, N. K., Nyhus, J., Oldre, A., Olson, E., Parente, J., Parker, P. D., Parry, S. E., Stevens, A., Pletikos, M., Reding, M., Roll, K., Sandman, D., Sarreal, M., Shapouri, S., Shapovalova, N. V., Shen, E. H., Sjoquist, N., Slaughterbeck, C. R., Smith, M., Sodt, A. J., Williams, D., Zollei, L., Fischl, B., Gerstein, M. B., Geschwind, D. H., Glass, I. A., Hawrylycz, M. J., Hevner, R. F., Huang, H., Jones, A. R., Knowles, J. A., Levitt, P., Phillips, J. W., Sestan, N., Wohnoutka, P., Dang, C., Bernard, A., Hohmann, J. G., & Lein, E. S. (2014). Transcriptional landscape of the prenatal human brain. Nature, 508, 199–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Imayoshi, I., & Kageyama, R. (2014). bHLH factors in self-renewal, multipotency, and fate choice of neural progenitor cells. Neuron, 82, 9–23.

    Article  CAS  PubMed  Google Scholar 

  33. Schuurmans, C., Armant, O., Nieto, M., Stenman, J. M., Britz, O., Klenin, N., Brown, C., Langevin, L. M., Seibt, J., Tang, H., Cunningham, J. M., Dyck, R., Walsh, C., Campbell, K., Polleux, F., & Guillemot, F. (2004). Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways. The EMBO Journal, 23, 2892–2902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Berninger, B., Guillemot, F., & Gotz, M. (2007). Directing neurotransmitter identity of neurones derived from expanded adult neural stem cells. The European Journal of Neuroscience, 25, 2581–2590.

    Article  PubMed  Google Scholar 

  35. Hattori, R., Kuchibhotla, K. V., Froemke, R. C., & Komiyama, T. (2017). Functions and dysfunctions of neocortical inhibitory neuron subtypes. Nature Neuroscience, 20, 1199–1208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Tyson, J. A., & Anderson, S. A. (2014). GABAergic interneuron transplants to study development and treat disease. Trends in Neurosciences, 37, 169–177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhu, Q., Naegele, J. R., & Chung, S. (2018). Cortical GABAergic interneuron/progenitor transplantation as a novel therapy for intractable epilepsy. Frontiers in Cellular Neuroscience, 12, 167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Shetty, A. K., & Bates, A. (2016). Potential of GABA-ergic cell therapy for schizophrenia, neuropathic pain, and Alzheimer's and Parkinson's diseases. Brain Research, 1638, 74–87.

    Article  CAS  PubMed  Google Scholar 

  39. Liu, Y., Liu, H., Sauvey, C., Yao, L., Zarnowska, E. D., & Zhang, S. C. (2013). Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells. Nature Protocols, 8, 1670–1679.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hirabayashi, Y., & Gotoh, Y. (2010). Epigenetic control of neural precursor cell fate during development. Nature Reviews. Neuroscience, 11, 377–388.

    Article  CAS  PubMed  Google Scholar 

  41. Dennis, D. J., Han, S., & Schuurmans, C. (2019). bHLH transcription factors in neural development, disease, and reprogramming. Brain Research, 1705, 48–65.

    Article  CAS  PubMed  Google Scholar 

  42. Sun, Y., Nadal-Vicens, M., Misono, S., Lin, M. Z., Zubiaga, A., Hua, X., Fan, G., & Greenberg, M. E. (2001). Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms. Cell, 104, 365–376.

    Article  CAS  PubMed  Google Scholar 

  43. Mizuguchi, R., Sugimori, M., Takebayashi, H., Kosako, H., Nagao, M., Yoshida, S., Nabeshima, Y., Shimamura, K., & Nakafuku, M. (2001). Combinatorial roles of olig2 and neurogenin2 in the coordinated induction of pan-neuronal and subtype-specific properties of motoneurons. Neuron, 31, 757–771.

    Article  CAS  PubMed  Google Scholar 

  44. Heinrich, C., Blum, R., Gascon, S., Masserdotti, G., Tripathi, P., Sanchez, R., Tiedt, S., Schroeder, T., Gotz, M., & Berninger, B. (2010). Directing astroglia from the cerebral cortex into subtype specific functional neurons. PLoS Biology, 8, e1000373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chouchane, M., & Costa, M. R. (2019). Instructing neuronal identity during CNS development and astroglial-lineage reprogramming: Roles of NEUROG2 and ASCL1. Brain Research, 1705, 66–74.

    Article  CAS  PubMed  Google Scholar 

  46. Aydin, B., Kakumanu, A., Rossillo, M., Moreno-Estelles, M., Garipler, G., Ringstad, N., Flames, N., Mahony, S., & Mazzoni, E. O. (2019). Proneural factors Ascl1 and Neurog2 contribute to neuronal subtype identities by establishing distinct chromatin landscapes. Nature Neuroscience, 22, 897–908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wilkinson, G., Dennis, D., & Schuurmans, C. (2013). Proneural genes in neocortical development. Neuroscience, 253, 256–273.

    Article  CAS  PubMed  Google Scholar 

  48. Brill, M. S., Ninkovic, J., Winpenny, E., Hodge, R. D., Ozen, I., Yang, R., Lepier, A., Gascon, S., Erdelyi, F., Szabo, G., Parras, C., Guillemot, F., Frotscher, M., Berninger, B., Hevner, R. F., Raineteau, O., & Gotz, M. (2009). Adult generation of glutamatergic olfactory bulb interneurons. Nature Neuroscience, 12, 1524–1533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Chen, X., Lepier, A., Berninger, B., Tolkovsky, A. M., & Herbert, J. (2012). Cultured subventricular zone progenitor cells transduced with neurogenin-2 become mature glutamatergic neurons and integrate into the dentate gyrus. PLoS One, 7, e31547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Fremeau, R. T., Jr., Troyer, M. D., Pahner, I., Nygaard, G. O., Tran, C. H., Reimer, R. J., Bellocchio, E. E., Fortin, D., Storm-Mathisen, J., & Edwards, R. H. (2001). The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron, 31, 247–260.

    Article  CAS  PubMed  Google Scholar 

  51. Avilion, A. A., Nicolis, S. K., Pevny, L. H., Perez, L., Vivian, N., & Lovell-Badge, R. (2003). Multipotent cell lineages in early mouse development depend on SOX2 function. Genes & Development, 17, 126–140.

    Article  CAS  Google Scholar 

  52. Adachi, K., Nikaido, I., Ohta, H., Ohtsuka, S., Ura, H., Kadota, M., Wakayama, T., Ueda, H. R., & Niwa, H. (2013). Context-dependent wiring of Sox2 regulatory networks for self-renewal of embryonic and trophoblast stem cells. Molecular Cell, 52, 380–392.

    Article  CAS  PubMed  Google Scholar 

  53. Favaro, R., Valotta, M., Ferri, A. L., Latorre, E., Mariani, J., Giachino, C., Lancini, C., Tosetti, V., Ottolenghi, S., Taylor, V., & Nicolis, S. K. (2009). Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nature Neuroscience, 12, 1248–1256.

    Article  CAS  PubMed  Google Scholar 

  54. Tontsch, S., Zach, O., & Bauer, H. C. (2001). Identification and localization of M-CoREST (1A13), a mouse homologue of the human transcriptional co-repressor CoREST, in the developing mouse CNS. Mechanisms of Development, 108, 165–169.

    Article  CAS  PubMed  Google Scholar 

  55. Dallman, J. E., Allopenna, J., Bassett, A., Travers, A., & Mandel, G. (2004). A conserved role but different partners for the transcriptional corepressor CoREST in fly and mammalian nervous system formation. The Journal of Neuroscience, 24, 7186–7193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Abrajano, J. J., Qureshi, I. A., Gokhan, S., Zheng, D., Bergman, A., & Mehler, M. F. (2009). REST and CoREST modulate neuronal subtype specification, maturation and maintenance. PLoS One, 4, e7936.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Abrajano, J. J., Qureshi, I. A., Gokhan, S., Zheng, D., Bergman, A., & Mehler, M. F. (2009). Differential deployment of REST and CoREST promotes glial subtype specification and oligodendrocyte lineage maturation. PLoS One, 4, e7665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Fuentes, P., Canovas, J., Berndt, F. A., Noctor, S. C., & Kukuljan, M. (2012). CoREST/LSD1 control the development of pyramidal cortical neurons. Cerebral Cortex, 22, 1431–1441.

    Article  PubMed  Google Scholar 

  59. Volvert, M. L., Prevot, P. P., Close, P., Laguesse, S., Pirotte, S., Hemphill, J., Rogister, F., Kruzy, N., Sacheli, R., Moonen, G., Deiters, A., Merkenschlager, M., Chariot, A., Malgrange, B., Godin, J. D., & Nguyen, L. (2014). MicroRNA targeting of CoREST controls polarization of migrating cortical neurons. Cell Reports, 7, 1168–1183.

    Article  CAS  PubMed  Google Scholar 

  60. Lopez, C. I., Saud, K. E., Aguilar, R., Berndt, F. A., Canovas, J., Montecino, M., & Kukuljan, M. (2016). The chromatin modifying complex CoREST/LSD1 negatively regulates notch pathway during cerebral cortex development. Developmental Neurobiology, 76, 1360–1373.

    Article  CAS  PubMed  Google Scholar 

  61. Lunyak, V. V., Prefontaine, G. G., & Rosenfeld, M. G. (2004). REST and peace for the neuronal-specific transcriptional program. Annals of the New York Academy of Sciences, 1014, 110–120.

    Article  CAS  PubMed  Google Scholar 

  62. Lunyak, V. V., Burgess, R., Prefontaine, G. G., Nelson, C., Sze, S. H., Chenoweth, J., Schwartz, P., Pevzner, P. A., Glass, C., Mandel, G., & Rosenfeld, M. G. (2002). Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science, 298, 1747–1752.

    Article  CAS  PubMed  Google Scholar 

  63. Roopra, A., Qazi, R., Schoenike, B., Daley, T. J., & Morrison, J. F. (2004). Localized domains of G9a-mediated histone methylation are required for silencing of neuronal genes. Molecular Cell, 14, 727–738.

    Article  CAS  PubMed  Google Scholar 

  64. Ballas, N., Grunseich, C., Lu, D. D., Speh, J. C., & Mandel, G. (2005). REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell, 121, 645–657.

    Article  CAS  PubMed  Google Scholar 

  65. Andres, M. E., Burger, C., Peral-Rubio, M. J., Battaglioli, E., Anderson, M. E., Grimes, J., Dallman, J., Ballas, N., & Mandel, G. (1999). CoREST: A functional corepressor required for regulation of neural-specific gene expression. Proceedings of the National Academy of Sciences of the United States of America, 96, 9873–9878.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zahr, S. K., Yang, G., Kazan, H., Borrett, M. J., Yuzwa, S. A., Voronova, A., Kaplan, D. R., & Miller, F. D. (2018). A translational repression complex in developing mammalian neural stem cells that regulates neuronal specification. Neuron, 97, 520–537 e6.

    Article  CAS  PubMed  Google Scholar 

  67. You, A., Tong, J. K., Grozinger, C. M., & Schreiber, S. L. (2001). CoREST is an integral component of the CoREST- human histone deacetylase complex. Proceedings of the National Academy of Sciences of the United States of America, 98, 1454–1458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hakimi, M. A., Bochar, D. A., Chenoweth, J., Lane, W. S., Mandel, G., & Shiekhattar, R. (2002). A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes. Proceedings of the National Academy of Sciences of the United States of America, 99, 7420–7425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Shi, Y. J., Matson, C., Lan, F., Iwase, S., Baba, T., & Shi, Y. (2005). Regulation of LSD1 histone demethylase activity by its associated factors. Molecular Cell, 19, 857–864.

    Article  CAS  PubMed  Google Scholar 

  70. Lee, M. G., Wynder, C., Cooch, N., & Shiekhattar, R. (2005). An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature, 437, 432–435.

    Article  CAS  PubMed  Google Scholar 

  71. Yang, M., Gocke, C. B., Luo, X., Borek, D., Tomchick, D. R., Machius, M., Otwinowski, Z., & Yu, H. (2006). Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase. Molecular Cell, 23, 377–387.

    Article  CAS  PubMed  Google Scholar 

  72. Shi, Y., Lan, F., Matson, C., Mulligan, P., Whetstine, J. R., Cole, P. A., Casero, R. A., & Shi, Y. (2004). Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell, 119, 941–953.

    Article  CAS  PubMed  Google Scholar 

  73. Fode, C., Ma, Q., Casarosa, S., Ang, S. L., Anderson, D. J., & Guillemot, F. (2000). A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes & Development, 14, 67–80.

    CAS  Google Scholar 

  74. Mattar, P., Langevin, L. M., Markham, K., Klenin, N., Shivji, S., Zinyk, D., & Schuurmans, C. (2008). Basic helix-loop-helix transcription factors cooperate to specify a cortical projection neuron identity. Molecular and Cellular Biology, 28, 1456–1469.

    Article  CAS  PubMed  Google Scholar 

  75. Britz, O., Mattar, P., Nguyen, L., Langevin, L. M., Zimmer, C., Alam, S., Guillemot, F., & Schuurmans, C. (2006). A role for proneural genes in the maturation of cortical progenitor cells. Cerebral Cortex, 16(Suppl 1), i138–i151.

    Article  PubMed  Google Scholar 

  76. Kovach, C., Dixit, R., Li, S., Mattar, P., Wilkinson, G., Elsen, G. E., Kurrasch, D. M., Hevner, R. F., & Schuurmans, C. (2013). Neurog2 simultaneously activates and represses alternative gene expression programs in the developing neocortex. Cerebral Cortex, 23, 1884–1900.

    Article  PubMed  Google Scholar 

  77. Roybon, L., Mastracci, T. L., Ribeiro, D., Sussel, L., Brundin, P., & Li, J. Y. (2010). GABAergic differentiation induced by Mash1 is compromised by the bHLH proteins Neurogenin2, NeuroD1, and NeuroD2. Cerebral Cortex, 20, 1234–1244.

    Article  PubMed  Google Scholar 

  78. Donega, V., Marcy, G., Lo Giudice, Q., Zweifel, S., Angonin, D., Fiorelli, R., Abrous, D. N., Rival-Gervier, S., Koehl, M., Jabaudon, D., & Raineteau, O. (2018). Transcriptional Dysregulation in postnatal Glutamatergic progenitors contributes to closure of the cortical neurogenic period. Cell Reports, 22, 2567–2574.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 31371507).

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  1. School of Medicine, Tongji University, No.1239, Siping Road, Shanghai, 200092, People’s Republic of China

    Yang Liu & Yuanyuan Zhang

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  1. Yang Liu
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Correspondence to Yang Liu.

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Figure S1

Confirmation of disruption of the ETV5 gene in human ETV5 KO ESCs. (A) Real-time quantitative PCR analysis of the ETV5 mRNA in WT and ETV5 KO ESCs. (B) Western blotting analysis of the ETV5 protein in ETV5 WT and KO ESCs. (PNG 78 kb)

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Figure S2

Relations between ETV5 and CoREST in NPCs and HEK293FT cells. (A) Real-time quantitative PCR analysis of the CoREST mRNA in WT and ETV5 KO NPCs. (B) Co-immunoprecipitation analysis of Flag-tagged ETV5 and HA-tagged CoREST in HEK293FT cell extracts. (PNG 118 kb)

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Liu, Y., Zhang, Y. ETV5 is Essential for Neuronal Differentiation of Human Neural Progenitor Cells by Repressing NEUROG2 Expression. Stem Cell Rev and Rep 15, 703–716 (2019). https://doi.org/10.1007/s12015-019-09904-4

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