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Baf-mediated transcriptional regulation of teashirt is essential for the development of neural progenitor cell lineages

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Accumulating evidence hints heterochromatin anchoring to the inner nuclear membrane as an upstream regulatory process of gene expression. Given that the formation of neural progenitor cell lineages and the subsequent maintenance of postmitotic neuronal cell identity critically rely on transcriptional regulation, it seems possible that the development of neuronal cells is influenced by cell type-specific and/or context-dependent programmed regulation of heterochromatin anchoring. Here, we explored this possibility by genetically disrupting the evolutionarily conserved barrier-to-autointegration factor (Baf) in the Drosophila nervous system. Through single-cell RNA sequencing, we demonstrated that Baf knockdown induces prominent transcriptomic changes, particularly in type I neuroblasts. Among the differentially expressed genes, our genetic analyses identified teashirt (tsh), a transcription factor that interacts with beta-catenin, to be closely associated with Baf knockdown-induced phenotypes that were suppressed by the overexpression of tsh or beta-catenin. We also found that Baf and tsh colocalized in a region adjacent to heterochromatin in type I NBs. Notably, the subnuclear localization pattern remained unchanged when one of these two proteins was knocked down, indicating that both proteins contribute to the anchoring of heterochromatin to the inner nuclear membrane. Overall, this study reveals that the Baf-mediated transcriptional regulation of teashirt is a novel molecular mechanism that regulates the development of neural progenitor cell lineages.

Abstract

Accumulating evidence hints heterochromatin anchoring to the inner nuclear membrane as an upstream regulatory process of gene expression. Given that the formation of neural progenitor cell lineages and the subsequent maintenance of postmitotic neuronal cell identity critically rely on transcriptional regulation, it seems possible that the development of neuronal cells is influenced by cell type-specific and/or context-dependent programmed regulation of heterochromatin anchoring. Here, we explored this possibility by genetically disrupting the evolutionarily conserved barrier-to-autointegration factor (Baf) in the Drosophila nervous system. Through single-cell RNA sequencing, we demonstrated that Baf knockdown induces prominent transcriptomic changes, particularly in type I neuroblasts. Among the differentially expressed genes, our genetic analyses identified teashirt (tsh), a transcription factor that interacts with beta-catenin, to be closely associated with Baf knockdown-induced phenotypes that were suppressed by the overexpression of tsh or beta-catenin. We also found that Baf and tsh colocalized in a region adjacent to heterochromatin in type I NBs. Notably, the subnuclear localization pattern remained unchanged when one of these two proteins was knocked down, indicating that both proteins contribute to the anchoring of heterochromatin to the inner nuclear membrane. Overall, this study reveals that the Baf-mediated transcriptional regulation of teashirt is a novel molecular mechanism that regulates the development of neural progenitor cell lineages.

참고문헌 (103)

  1. Deneris, E. S., "Maintenance of postmitotic neuronal cell identity", Nat. Neurosci, 17, pp.899~907 (2014)
  2. Whyte, W. A., "Master transcription factors and mediator establish super enhancers at key cell identity genes", Cell, 153, pp.307~319 (2013)
  3. Almeida, N., "Employing core regulatory circuits to define cell identity", EMBO J, 40, pp.e106785~ (2021)
  4. Doe, C. Q., "Temporal patterning in the Drosophila CNS", Annu. Rev. Cell Dev. Biol, 33, pp.219~240 (2017)
  5. Holguera, I., "Neuronal specification in space and time", Science, 362, pp.176~180 (2018)
  6. Grosskortenhaus, R., "Pdm and Castor specify late-born motor neuron identity in the NB7-1 lineage", Genes Dev, 20, pp.2618~2627 (2006)
  7. Isshiki, T., "Drosophila neuroblasts sequentially express transcription factors which specify the temporal identity of their neuronal progeny", Cell, 106, pp.511~521 (2001)
  8. Jafari, S., "Combinatorial activation and repression by seven transcription factors specify Drosophila odorant receptor expression", PLoS Biol, 10, pp.e1001280~ (2012)
  9. Harr, J. C., "Histones and histone mod ifications in perinuclear chromatin anchoring : from yeast to man", EMBO Rep, 17, pp.139~155 (2016)
  10. Zheng, H., "The role of 3D genome organization in development and cell differentiation", Nat. Rev. Mol. Cell Biol, 20, pp.535~550 (2019)
  11. Kishi, Y., "Regulation of chromatin structure during neural develop ment", Front Neurosci, 12, pp.874~ (2018)
  12. Ye, Y., "Chromatin remodeling during in vivo neural stem cells differentiating to neurons in early Drosophila embryos", Cell Death Differ, 24, pp.409~420 (2017)
  13. Chathoth, K. T., "Chromatin architecture reorganization during neuronal cell differentiation in Drosophila genome", Genome Res, 29, pp.613~625 (2019)
  14. Dixon, J. R., "Chromatin architecture reorganization during stem cell dif ferentiation", Nature, 518, pp.331~336 (2015)
  15. Zhao, R., "Nuclear neighborhoods and gene expression", Curr. Opin. Genet Dev, 19, pp.172~179 (2009)
  16. Guerreiro, I., "Spatial chromatin organization and gene regulation at the nuclear lamina", Curr. Opin. Genet Dev, 55, pp.19~25 (2019)
  17. Montes de Oca, R., "Barrier-to-Autointegration Factor influences specific histone modifications", Nucleus, 2, pp.580~590 (2011)
  18. Oh, H. S., "Barrier-to-autointegration factor 1 (BAF", BANF1) promotes association of the SETD1A histone methyltransferase with herpes simplex virus immediate-early gene promoters, 2015, pp.6, e00345–00315~
  19. Montes de Oca, R., "Binding of barrier to autointegration factor (BAF) to histone H3 and selected linker histones including H1.1", J. Biol. Chem, 280, pp.42252~42262 (2005)
  20. Dunlevy, K. L., "The PRR14 heterochromatin tether encodes modular domains that mediate and regulate nuclear lamina targeting", J. Cell Sci (2020)[DOI]
  21. Bian, Q., "Histone H3K9 methylation promotes formation of genome compartments in Caenorhabditis elegans via chromosome compaction and perinuclear anchoring", Proc. Natl Acad. Sci. USA, 117, pp.11459~11470 (2020)
  22. Gonzalez-Sandoval, A., "Perinuclear anchoring of H3K9-methylated chro matin stabilizes induced cell fate in C", Cell, 163, pp.1333~1347 (2015)
  23. Furukawa, K., "LAP2 binding protein 1(L2BP1", BAF)is a candidate mediator of LAP2-chromatin interaction, 1999, pp.112, 2485~2492
  24. Mansharamani, M., "Direct binding of nuclear membrane protein MAN1toemerin in vitro and two modes of binding to barrier-to-autointegration factor", J. Biol. Chem, 280, pp.13863~13870 (2005)
  25. Lee, K. K., "Distinct functional domains in emerin bind lamin A and DNA bridging protein BAF", J. Cell Sci, 114, pp.4567~4573 (2001)
  26. Samwer, M., "DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes", Cell, 170, pp.956~972 (2017)
  27. Poleshko, A., "The human protein PRR14 tethers heterochromatin to the nuclear lamina during interphase and mitotic exit", Cell Rep, 5, pp.292~301 (2013)
  28. Gorjanacz, M., "Caenorhabditis elegans BAF-1 and its kinase VRK-1 partici pate directly in post-mitotic nuclear envelope assembly", EMBO J, 26, pp.132~143 (2007)
  29. Margalit, A., "Barrier to autointegration factor blocks premature cell fusion and maintains adult muscle integrity in C", J. Cell Biol, 178, pp.661~673 (2007)
  30. Yang, M., "A novel role of PRR14 in the regulation of skeletal myogenesis", Cell Death Dis, 6, pp.e1734~ (2015)
  31. Segura-Totten, M., "BAF : roles in chromatin, nuclear structure and retrovirus integration", Trends Cell Biol, 14, pp.261~266 (2004)
  32. Furukawa, K., "Barrier-to-autointegration factor plays crucial roles in cell cycle progression and nuclear organization in Drosophila", J. Cell Sci, 116, pp.3811~3823 (2003)
  33. Homem, C. C., "Long-term live cell imaging and automated 4D analysis of drosophila neuroblast lineages", PLoS ONE, 8, pp.e79588~ (2013)
  34. Ceron, J., "A primary cell culture of Drosophila post embryonic larval neuroblasts to study cell cycle and asymmetric division", Eur. J. Cell Biol, 85, pp.567~575 (2006)
  35. Kwon, M. J., "Coiled-coil structure-dependent interactions between polyQ proteins and Foxo lead to dendrite pathology and behavioral defects", Proc. Natl Acad. Sci. USA, 115, pp.E10748~E10757 (2018)
  36. Chung, C. G., "Golgi outpost synthesis impaired by toxic polyglutamine proteins contributes to dendritic pathology in neurons", Cell Rep, 20, pp.356~369 (2017)
  37. Rosenberg, A. B., "Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding", Science, 360, pp.176~182 (2018)
  38. Parekh, S., "zUMIs—a fast and f lexible pipeline to process RNA sequencing data with UMIs", Gigascience (2018)[DOI]
  39. Dobin, A., "STAR : ultrafast universal RNA-seq aligner", Bioinformatics, 29, pp.15~21 (2013)
  40. McCarthy, D. J., "Scater : pre-processing, quality control, normalization and visualization of single-cell RNA-seq data in R", Bioinformatics, 33, pp.1179~1186 (2017)
  41. Lun, A. T., "step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor", F1000Res, 5, pp.2122~ (2016)
  42. Satija, R., "Spatial reconstruction of single-cell gene expression data", Nat. Biotechnol, 33, pp.495~502 (2015)
  43. Ritchie, M. E., "limma powers differential expression analyses for RNA sequencing and microarray studies", Nucleic Acids Res, 43, pp.e47~ (2015)
  44. Skinnider, M. A., "Cell type prioritization in single-cell data", Nat. Biotechnol, 39, pp.30~34 (2020)
  45. Setty, M., "Characterization of cell fate probabilities in single-cell data with Palantir", Nat. Biotechnol, 37, pp.451~460 (2019)
  46. Alpert, A., "Alignment of single-cell trajec tories to compare cellular expression dynamics", Nat. Methods, 15, pp.267~270 (2018)
  47. Brunet Avalos, C., "Single cell transcriptome atlas of the Drosophila larval brain", Elife (2019)[DOI]
  48. Bier, E., "deadpan, an essential pan-neural gene in Drosophila, encodes a helix-loop-helix protein similar to the hairy gene product", Genes Dev, 6, pp.2137~2151 (1992)
  49. Bowman, S. K., "The tumor suppressors Brat and Numb regulate transit amplifying neuroblast lineages in Drosophila", Dev. Cell, 14, pp.535~546 (2008)
  50. Zhu, S., "Ets transcription factor Pointed promotes the generation of intermediate neural progenitors in Dro sophila larval brains", Proc. Natl Acad. Sci. USA, 108, pp.20615~20620 (2011)
  51. Hirata, J., "Asymmetric segregation of the homeodomain protein Prospero during Drosophila development", Nature, 377, pp.627~630 (1995)
  52. Caussinus, E., "Asymmetric stem cell division in development and cancer", Prog. Mol. Subcell. Biol, 45, pp.205~225 (2007)
  53. Rives-Quinto, N., "Sequential activation of transcriptional repressors pro motes progenitor commitment by silencing stem cell identity genes", Elife (2020)[DOI]
  54. Corrales, M., "A single-cell transcriptomic atlas of complete insect nervous systems across multiple life stages", Neural Dev, 17, pp.8~ (2022)
  55. Dillon, N., "Single cell RNA-seq analysis reveals temporally-regulated and quiescence-regulated gene expression in Drosophila larval neuroblasts", Neural Dev, 17, pp.7~ (2022)
  56. Bannister, A. J., "Regulation of chromatin by histone modifications", Cell Res, 21, pp.381~395 (2011)
  57. Weng, R., "Control of Drosophila Type I and Type II central brain neuroblast proliferation by bantam microRNA", Development, 142, pp.3713~3720 (2015)
  58. Torras-Llort, M., "A fraction of barrier-to-autointegration factor(BAF)associates with centromeres and controls mitosis progression", Commun. Biol, 3, pp.454~ (2020)
  59. Duan, T., "Survival of Drosophila germline stem cells requires the chromatin-binding protein Barrier-to-autointegration factor", Development (2020)[DOI]
  60. Levine, M. S., "The impact of mitotic errors on cell proliferation and tumorigenesis", Genes Dev, 32, pp.620~638 (2018)
  61. Hans, F., "Histone H3 phosphorylation and cell division", Oncogene, 20, pp.3021~3027 (2001)
  62. Wolf, F. A., "PAGA : graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells", Genome Biol, 20, pp.59~ (2019)
  63. Kohwi, M., "Temporal fate specification and neural progenitor competence during development", Nat. Rev. Neurosci, 14, pp.823~838 (2013)
  64. Skeath, J. B., "Genetic control of Drosophila nerve cord development", Curr. Opin. Neurobiol, 13, pp.8~15 (2003)
  65. Bahrampour, S., "Neural lineage progression controlled by a temporal proliferation program", Dev. Cell, 43, pp.332~348 (2017)
  66. Jacobs, H. W., "A complex degradation signal in Cyclin A required for G1 arrest, and a C-terminal region for mitosis", EMBO J, 20, pp.2376~2386 (2001)
  67. Royzman, I., "Mutations in Drosophila DP and E2F distinguish G1-S progression from an associated transcriptional program", Genes Dev, 11, pp.1999~2011 (1997)
  68. Ner, S. S., "HMG-D, the Drosophila melanogaster homologue of HMG 1protein, is associated with early embryonic chromatin in the absence of histone H1", EMBO J, 13, pp.1817~1822 (1994)
  69. Chalkley, G. E., "The transcriptional coactivator SAYP is a trithorax group signature subunit of the PBAP chromatin remodeling complex", Mol. Cell Biol, 28, pp.2920~2929 (2008)
  70. Quinn, L. M., "Drosophila Hfp negatively regulates dmyc and stg to inhibit cell proliferation", Development, 131, pp.1411~1423 (2004)
  71. Homem, C. C. F., "Ecdysone and mediator change energy metabolism to terminate proliferation in Drosophila neural stem cells", Cell, 158, pp.874~888 (2014)
  72. Atwood, S. X., "aPKC phosphorylates Miranda to polarize fate determinants during neuroblast asymmetric cell division", Curr. Biol, 19, pp.723~729 (2009)
  73. Prehoda, K. E., "Polarization of Drosophila neuroblasts during asymmetric division", Cold Spring Harb. Perspect. Biol, 1, pp.a001388~ (2009)
  74. Oon, C. H., "Asymmetric recruitment and actin-dependent cortical f lows drive the neuroblast polarity cycle", Elife (2019)[DOI]
  75. Rolls, M. M., "Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia", J. Cell Biol, 163, pp.1089~1098 (2003)
  76. Lee, C. Y., "Lgl, Pins and aPKC regulate neuroblast self renewal versus differentiation", Nature, 439, pp.594~598 (2006)
  77. Shen, C. P., "Miranda is required for the asymmetric loca lization of Prospero during mitosis in Drosophila", Cell, 90, pp.449~458 (1997)
  78. Guo, L., "Descending neurons coordinate anterior grooming behavior in Drosophila", Curr. Biol, 32, pp.823~833 (2022)
  79. Hampel, S., "A neural command circuit for grooming movement control", Elife, 4, pp.e08758~ (2015)
  80. McGuire, S. E., "Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila", Sci. STKE, pp.pl6~ (2004)
  81. Gallet, A., "The C-terminal domain of armadillo binds to hypopho sphorylated teashirt to modulate wingless signalling in Drosophila", EMBO J, 18, pp.2208~2217 (1999)
  82. Gallet, A., "Trunk-specific mod ulation of wingless signalling in Drosophila by teashirt binding to armadillo", Curr. Biol, 8, pp.893~902 (1998)
  83. Vishal, K., "Adult muscle formation requires drosophila moleskin for pro liferation of wing disc-associated muscle precursors", Genetics, 206, pp.199~213 (2017)
  84. Rosenbloom, A. B., "beta-Catenin signaling dynamics regulate cell fate in differentiating neural stem cells", Proc. Natl Acad. Sci. USA, 117, pp.28828~28837 (2020)
  85. Tian, A., "Regulation of stem cell pro liferation and cell fate specification by wingless", Wnt signaling gradients enri ched at adult intestinal compartment boundaries, 2016, pp.12, e1005822~
  86. Pai, L. M., "Negative regulation of Armadillo, a Wingless effector in Drosophila", Development, 124, pp.2255~2266 (1997)
  87. Meister, P., "The spatial dynamics of tissue-specific promoters during C. elegans development", Genes Dev, 24, pp.766~782 (2010)
  88. Snyder, M. J., "Anchoring of heterochromatin to the nuclear lamina rein forces dosage compensation-mediated gene repression", PLoS Genet, 12, pp.e1006341~ (2016)
  89. Kafri, P., "Quantifying beta-catenin subcellular dynamics and cyclin D1mRNA transcription during Wnt signaling in single living cells", Elife (2016)[DOI]
  90. Fagotto, F., "Looking beyond the Wnt pathway for the deep nature of beta catenin", EMBO Rep, 14, pp.422~433
  91. Brand, A. H., "Neural stem cell biology in vertebrates and inver tebrates: more alike than different?", Neuron, 70, pp.719~729 (2011)
  92. Homem, C. C., "Proliferation control in neural stem and progenitor cells", Nat. Rev. Neurosci, 16, pp.647~659 (2015)
  93. Noctor, S. C., "Neurons derived from radial glial cells establish radial units in neocortex", Nature, 409, pp.714~720 (2001)
  94. Miyata, T., "Asymmetric inheritance of radial glial fibers by cortical neurons", Neuron, 31, pp.727~741 (2001)
  95. Franco, S. J., "Shaping our minds: stem and progenitor cell diversity in the mammalian neocortex", Neuron, 77, pp.19~34 (2013)
  96. Shen, Q., "The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells", Nat. Neurosci, 9, pp.743~751 (2006)
  97. Cox, J. L., "Banf1 is required to maintain the self-renewal of both mouse and human embryonic stem cells", J. Cell Sci, 124, pp.2654~2665 (2011)
  98. Kuerbitz, J., "Loss of intercalated cells(ITCs)in the mouse amygdala of Tshz1mutants correlates with fear, depression, and social interaction phenotypes", J. Neurosci, 38, pp.1160~1177 (2018)
  99. Ragancokova, D., "TSHZ1-dependent gene regulation is essential for olfactory bulb development and olfaction", J. Clin. Invest, 124, pp.1214~1227 (2014)
  100. Lorenzen, J. A., "Nuclear import of activated D-ERK by DIM-7, an importin family member encoded by the gene moleskin", Development, 128, pp.1403~1414 (2001)
  101. James, B. P., "Nuclear localization of the ERK MAP kinase mediated by Drosophila alphaPS2betaPS integrin and importin-7", Mol. Biol. Cell, 18, pp.4190~4199 (2007)
  102. Lanctot, A. A., "Spatially dependent dynamic MAPK modulation by the Nde1-Lis1-Brap complex patterns mammalian CNS", Dev. Cell, 25, pp.241~255 (2013)
  103. Wang, Y., "ERK inhibition rescues defects in fate specification of Nf1deficient neural progenitors and brain abnormalities", Cell, 150, pp.816~830 (2012)

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