2010 Fiscal Year Final Research Report
Global regulation of the chromatin state of neural progenitors during development
| Project/Area Number |
20241044
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
基礎ゲノム科学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
GOTOH Yukiko 東京大学, 分子細胞生物学研究所, 教授 (70252525)
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| Project Period (FY) |
2008 – 2010
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| Keywords | クロマチン / 神経幹細胞 |
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| Research Abstract |
Neurons, astrocytes and oligodendrocytes, three major cell types that consist the central nervous system, are derived from common neural stem cells(NSCs). Whereas NSCs generate neurons in the early stages of neocortical development, they lose the neurogenic potential and generate only glial cells in the late stages. In this study, we found "global" changes of the chromatin state in NPCs during neocortical development in addition to "local" changes at specific gene loci. Chromatins isolated from early-stage NSCs were less condensed compared to those from late-stage NSCs, as revealed by nuclease digestion and salt-extraction analyses, as well as by a fluorescent recovery after photobleaching(FRAP) analysis using histone H1-GFP. We also identified chromatin-binding proteins necessary for the "less condensed" state of the chromatin in early-stage NSCs. Importantly, knockdown of these proteins reduced the neurogenic capacity of early-stage NSCs, and conversely, their overexpression increase
… More
d neurogenesis and suppressed astrogenesis of late-stage NSCs. These results suggest that global chromatin condensation might contribute to the fate restriction of NSCs during neocortical development.
Recent studies have revealed various biological functions for repetitive sequences, which make up about half of the human genome. One such sequence, major satellites, which are tandem repetitive sequences adjacent to the centromere, have been shown to be a kinetochore component that plays a role in the formation and function of the pericentric heterochromatin necessary for mitosis. However, it is unknown whether these regions also play a role in post-mitotic cells. Here, we show that, during neuronal differentiation, the heterochromatin domains that include major satellite regions become both enriched with the active histone modification lysine-4 trimethylation of histone H3, and more sensitive to nuclease, both of which suggest increased activation of this area. Further supporting this notion, we also found that transcription from major satellite regions is significantly increased during neuronal differentiation both in vitro and in vivo. These results together suggest that the structural and transcriptional state of major satellite regions changes dramatically during neuronal differentiation, implying that this region might play a role in differentiating neurons. Less
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Research Products
(49 results)
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[Journal Article] Wnt signaling and its downstream target N-myc regulate basal progenitors in the developing neocortex2010
Author(s)
Kuwahara, A., Hirabayashi, Y., Knoepfler, P. S., Taketo, M. M., Sakai, J., Kodama, T. and Gotoh, Y.
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Journal Title
Development
Volume: 137
Pages: 1035-1044
Peer Reviewed
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[Journal Article] Polycomb limits the neurogenic competence of neural precursor cells to promote astrogenic fate transition2009
Author(s)
Hirabayashi, Y., Suzki, N., Tsuboi, M., Endo, T. A., Toyoda, T., Shinga, J., Koseki, H., Vidal, M. and Gotoh, Y.
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Journal Title
Neuron
Volume: 63
Pages: 600-613
Peer Reviewed
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[Journal Article] Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash12009
Author(s)
Oishi, K., Watatani, K., Itoh, Y., Okano, H., Guillemot, F., Nakajima, K. and Gotoh, Y.
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Journal Title
Proc. Natl. Acad. Sci.
Volume: 106
Pages: 13064-13069
Peer Reviewed
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[Presentation] ASK family kinases discriminate between interferon production and apoptosis in antiviral response2011
Author(s)
Tomohiko Okazaki, Maiko Higuchi, Kohsuke Takeda, Makoto Miyagishi, Atsushi Kato, Mitsutoshi Yoneyama, Takashi Fujita, Hidenori Ichijo, and Yukiko Gotoh
Organizer
Todai Forum 2011, Forum on Systems Biology & Genomic Medicine
Place of Presentation
Institut Pasteur, Paris, FRANCE
Year and Date
20111017-18
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[Presentation] The ASK family discriminates between interferon production and apoptosis in antiviral response(oral and poster)2011
Author(s)
Tomohiko Okazaki, Maiko Higuchi, Kohsuke Takeda, Makoto Miyagishi, Atsushi Kato, Mitsutoshi Yoneyama, Takashi Fujita, Hidenori Ichijo, and Yukiko Gotoh
Organizer
13th International TNF Conference
Place of Presentation
Awaji Yumebutai International Conference Center, Hyogo, JAPAN
Year and Date
20110515-18
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[Presentation] Temporal Regulation of Cortical Neural Precursor Cell Fate by Polycomb Group Proteins2011
Author(s)
Hirabayashi, Y., Suzki, N., Tsuboi, M., Miguel Vidal, Koseki, H., and Gotoh, Y.
Organizer
CDB Symposium 2011
Place of Presentation
Kobe, Japan
Year and Date
20110314-15
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[Presentation] The ASK MAPKKK family mediates host defense responses against viral infection2010
Author(s)
Okazaki, T., Higuchi, M., Takeda, K., Miyagishi, M., Kato, A., Yoneyama, M., Fujita, T., Ichijo, H., and Gotoh, Y
Organizer
14th International Congress of Immunology
Place of Presentation
The Kobe Convention Center Complex, Kobe, Japan
Year and Date
20100816-20
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[Presentation] Temporal regulation of cortical neural precursor cell fate by polycomb group proteins2010
Author(s)
Hirabayashi, Y., Suzki, N., Tsuboi, M., Miguel Vidal, Koseki, H., Gotoh, Y.
Organizer
Keystone Symposium-Dynamics of Eukaryotic Transcription during Development
Place of Presentation
Big Sky, USA
Year and Date
20100407-12
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[Presentation] Global a go-go!2010
Author(s)
Yusuke Kishi, Yuki Fujii, Hiroaki Oshiro, Yusuke Hirabayashi, Yukiko Gotoh
Organizer
2nd German-Japanese Bilateral Event on Neural Stem Cells and Mammalian Neurogenesis
Place of Presentation
Spreewald, Germany
Year and Date
2010-07-16
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