Yusuke Miyanari Lab

Division of Nulcear Dynamics

Okazaki Institute for Integrative Bioscience

Yusuke Miyanari Lab

Division of Nulcear Dynamics

Okazaki Institute for Integrative Bioscience

Yusuke Miyanari Lab

Division of Nulcear Dynamics

Okazaki Institute for Integrative Bioscience

Uncovering the secrets of reprogramming

A fundamental question in biology is to understand the mechanisms underlying cell-fate decision. Genomic reprogramming after mammalian fertilization reverts terminally differentiated gametes into toti- or pluri-potent states to start a new developmental program. Cell lineage allocation in the reprogramming process is accompanied by drastic changes in the pattern of gene expression, epigenetic configurations, and nuclear organization. We aim to reveal the roles of chromatin dynamics in cell lineage-allocation by deciphering the molecular mechanisms underlying remodeling of nuclear organization and their effects on developmental gene expression, using mouse embryos and embryonic stem (ES) cells as model systems.

Uncovering the secret of reprogramming

A fundamental question in biology is to understand the mechanisms underlying cell-fate decision. Genomic reprogramming after mammalian fertilization reverts terminally differentiated gametes into toti- or pluri-potent states to start a new developmental program. Cell lineage allocation in the reprogramming process is accompanied by drastic changes in the pattern of gene expression, epigenetic configurations, and nuclear organization. We aim to reveal the roles of chromatin dynamics in cell lineage-allocation by deciphering the molecular mechanisms underlying remodeling of nuclear organization and their effects on developmental gene expression, using mouse embryos and embryonic stem (ES) cells as model systems.

Uncovering the secrets of reprogramming

A fundamental question in biology is to understand the mechanisms underlying cell-fate decision. Genomic reprogramming after mammalian fertilization reverts terminally differentiated gametes into toti- or pluri-potent states to start a new developmental program. Cell lineage allocation in the reprogramming process is accompanied by drastic changes in the pattern of gene expression, epigenetic configurations, and nuclear organization. We aim to reveal the roles of chromatin dynamics in cell lineage-allocation by deciphering the molecular mechanisms underlying remodeling of nuclear organization and their effects on developmental gene expression, using mouse embryos and embryonic stem (ES) cells as model systems.

Research topics

Understanding reprogramming process in early mouse development
Genomic reprogramming reverts fully differentiated germ cells to a totipotent state to start a new developmental program. In early mouse embryos, terminally differentiated gametes are reprogrammed after fertilization thereby acquiring a totipotent state. Upon the fourth cleavage, 8-cell stage embryos, which have undergone the process of compaction, will give rise to the morula. The outer cells of the morula will differentiate into the epithelial trophectoderm (TE) of the blastocyst. The inner cells of the morula will become the inner cell mass (ICM) of the blastocyst. The ICM subsequently leads to the formation of two lineages, epiblast (EPI) and primitive endoderm (PE). The processe of lineage allocation is regulated by key transcription factors such as Nanog, Oct4, Cdx2, and Gata6. We aim to understand how these factors are transcriptionally activated by focusing epigenetic modifications and nuclear architecture.
Higher order of chromatin structure
Mammalian genomes are strictly organized within nuclear space. Spatiotemporal organization of genomic DNA within the nucleus is suggested as an emerging key player to regulate gene expression. The developmental program accompanies nuclear remodeling, resulting in construction of cell-type specific nuclear architecture. Firstly, chromosomes are confined in discrete nuclear spaces, “chromosome territories”. Within them, further levels of 3D organization, “topologically associating domains” (TADs), are observed. TADs can be defined as linear units of chromatin containing several gene loci, and fold as discrete 3D structures in which gene loci frequently interact with each other. Recent works have revealed that folding of “local” chromatin structures such as enhancer-promoter looping is associated with genome functions. Despite the drastic changes of these hierarchical chromatin structures, their role in cell-fate decision remains largely unexplored. We aim to reveal roles of nuclear dynamics in cell lineage-allocation by deciphering the molecular mechanisms underlying remodeling of nuclear organization. We are also trying to develop new technologies to address chromatin signature in living cells.
Live imaging of chromatin dymamics
Chromatin is organized in a non-random fashion within three-dimensional nuclear space. During developmental process, nuclear architecture is dramatically reconstructed, resulting in establishment of cell-type specific nuclear organization. Defects in structural components of the nucleus are responsible for developmental aberrations and several human diseases. Remodeling of nuclear architecture leads to spatial arrangement of genes, which could affect genome functions including gene expression. However regulatory mechanism underlying nuclear reorganization during cell-fate decision remains largely unknown. Live imaging of nuclear remodeling would be a breakthrough toward uncovering the functional relevance and mechanisms regulating genome architecture. We have developed a powerful imaging technology termed TALE-mediated Genome Visualization (TGV), which allows us to track specific genomic sequences in living cells (Miyanari Y, Nature Structural & Molecular Biology, 2013). Importantly, this technique can be extended to versatile and robust applications, which will be integrated into our study to manipulate several genome functions. We aim to understand the effects of nuclear remodeling onto gene expression and cell-lineage allocation.
Heterogeneity

Research topics

Understanding reprogramming process in early mouse development
Genomic reprogramming reverts fully differentiated germ cells to a totipotent state to start a new developmental program. In early mouse embryos, terminally differentiated gametes are reprogrammed after fertilization thereby acquiring a totipotent state. Upon the fourth cleavage, 8-cell stage embryos, which have undergone the process of compaction, will give rise to the morula. The outer cells of the morula will differentiate into the epithelial trophectoderm (TE) of the blastocyst. The inner cells of the morula will become the inner cell mass (ICM) of the blastocyst. The ICM subsequently leads to the formation of two lineages, epiblast (EPI) and primitive endoderm (PE). The processe of lineage allocation is regulated by key transcription factors such as Nanog, Oct4, Cdx2, and Gata6. We aim to understand how these factors are transcriptionally activated by focusing epigenetic modifications and nuclear architecture.
Higher order of chromatin structure
Mammalian genomes are strictly organized within nuclear space. Spatiotemporal organization of genomic DNA within the nucleus is suggested as an emerging key player to regulate gene expression. The developmental program accompanies nuclear remodeling, resulting in construction of cell-type specific nuclear architecture. Firstly, chromosomes are confined in discrete nuclear spaces, “chromosome territories”. Within them, further levels of 3D organization, “topologically associating domains” (TADs), are observed. TADs can be defined as linear units of chromatin containing several gene loci, and fold as discrete 3D structures in which gene loci frequently interact with each other. Recent works have revealed that folding of “local” chromatin structures such as enhancer-promoter looping is associated with genome functions. Despite the drastic changes of these hierarchical chromatin structures, their role in cell-fate decision remains largely unexplored. We aim to reveal roles of nuclear dynamics in cell lineage-allocation by deciphering the molecular mechanisms underlying remodeling of nuclear organization. We are also trying to develop new technologies to address chromatin signature in living cells.
Live imaging of chromatin dymamics
Chromatin is organized in a non-random fashion within three-dimensional nuclear space. During developmental process, nuclear architecture is dramatically reconstructed, resulting in establishment of cell-type specific nuclear organization. Defects in structural components of the nucleus are responsible for developmental aberrations and several human diseases. Remodeling of nuclear architecture leads to spatial arrangement of genes, which could affect genome functions including gene expression. However regulatory mechanism underlying nuclear reorganization during cell-fate decision remains largely unknown. Live imaging of nuclear remodeling would be a breakthrough toward uncovering the functional relevance and mechanisms regulating genome architecture. We have developed a powerful imaging technology termed TALE-mediated Genome Visualization (TGV), which allows us to track specific genomic sequences in living cells (Miyanari Y, Nature Structural & Molecular Biology, 2013). Importantly, this technique can be extended to versatile and robust applications, which will be integrated into our study to manipulate several genome functions. We aim to understand the effects of nuclear remodeling onto gene expression and cell-lineage allocation.
Heterogeneity

Research topics

Understanding reprogramming process in early mouse development
Genomic reprogramming reverts fully differentiated germ cells to a totipotent state to start a new developmental program. In early mouse embryos, terminally differentiated gametes are reprogrammed after fertilization thereby acquiring a totipotent state. Upon the fourth cleavage, 8-cell stage embryos, which have undergone the process of compaction, will give rise to the morula. The outer cells of the morula will differentiate into the epithelial trophectoderm (TE) of the blastocyst. The inner cells of the morula will become the inner cell mass (ICM) of the blastocyst. The ICM subsequently leads to the formation of two lineages, epiblast (EPI) and primitive endoderm (PE). The processe of lineage allocation is regulated by key transcription factors such as Nanog, Oct4, Cdx2, and Gata6. We aim to understand how these factors are transcriptionally activated by focusing epigenetic modifications and nuclear architecture.
Higher order of chromatin structure
Mammalian genomes are strictly organized within nuclear space. Spatiotemporal organization of genomic DNA within the nucleus is suggested as an emerging key player to regulate gene expression. The developmental program accompanies nuclear remodeling, resulting in construction of cell-type specific nuclear architecture. Firstly, chromosomes are confined in discrete nuclear spaces, “chromosome territories”. Within them, further levels of 3D organization, “topologically associating domains” (TADs), are observed. TADs can be defined as linear units of chromatin containing several gene loci, and fold as discrete 3D structures in which gene loci frequently interact with each other. Recent works have revealed that folding of “local” chromatin structures such as enhancer-promoter looping is associated with genome functions. Despite the drastic changes of these hierarchical chromatin structures, their role in cell-fate decision remains largely unexplored. We aim to reveal roles of nuclear dynamics in cell lineage-allocation by deciphering the molecular mechanisms underlying remodeling of nuclear organization. We are also trying to develop new technologies to address chromatin signature in living cells.
Live imaging of chromatin dymamics
Chromatin is organized in a non-random fashion within three-dimensional nuclear space. During developmental process, nuclear architecture is dramatically reconstructed, resulting in establishment of cell-type specific nuclear organization. Defects in structural components of the nucleus are responsible for developmental aberrations and several human diseases. Remodeling of nuclear architecture leads to spatial arrangement of genes, which could affect genome functions including gene expression. However regulatory mechanism underlying nuclear reorganization during cell-fate decision remains largely unknown. Live imaging of nuclear remodeling would be a breakthrough toward uncovering the functional relevance and mechanisms regulating genome architecture. We have developed a powerful imaging technology termed TALE-mediated Genome Visualization (TGV), which allows us to track specific genomic sequences in living cells (Miyanari Y, Nature Structural & Molecular Biology, 2013). Importantly, this technique can be extended to versatile and robust applications, which will be integrated into our study to manipulate several genome functions. We aim to understand the effects of nuclear remodeling onto gene expression and cell-lineage allocation.
Heterogeneity

Member

Member

Member

Publications

Miyanari Y

TAL effector-mediated Genome Visualization (TGV)

Methods, 2014, Sep;69(2):198-204.

 

Miyanari Y*, Birling CZ. And Torres-Padilla ME*

Live visualization of chromatin dynamics using fluorescent TALEs

Nature Structural & Molecular Biology, 2013

*Corresponding authors    * Highlighted by Nature Methods

 

Li Y*, Miyanari Y*, Shirane K, Nitta H, Kubota T, Ohashi H, Okamoto A, Sasaki H.

Sequence-specific microscopic visualization of DNA methylation status at satellite repeats in individual cell nuclei and chromosomes

Nucleic Acids Research, 2013  *Equal contribution

 

Miyanari Y, Torres-Padilla ME. Control of ground-state pluripotency by allelic regulation of Nanog.

Nature. 483.470-473. 2012

 

Miyanari Y, Torres-Padilla ME. 

Epigenetic regulation of reprogramming factors towards pluripotency in mouse preimplantation development. 

Curr Opin Endocrinol Diabetes Obes. 500-506.2010. Review

 

Hiura H, Sugawara A, Ogawa H, John RM, Miyauchi N, Miyanari Y, Horiike T, Li Y, Yaegashi N, Sasaki H, Kono T, Arima T. 

A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip. 

Nucleic Acids Res. 38:4929-45.2010.

 

Hishiki T, Shimizu Y, Tobita R, Sugiyama K, Ogawa K, Funami K, Ohsaki Y, Fuji moto T, Takaku H, Wakita T, Baumert TF, Miyanari Y, Shimotohno K. 

Infectivity of hepatitis C virusz is influenced by association with apolipoprotein E isoforms. 

J. Virol.84.12048-57. 2010. 

 

Ogawa K, Hishiki T, Shimizu Y, Funami K, Sugiyama K, Miyanari Y, Shimotohno K.

Hepatitis C virus utilizes lipid droplet for production of infectious virus.

Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(7):217-28. Review.

 

Miyanari Y, Atsuzawa K, Usuda N, Watashi K, Hishiki T, Zayas M, Bartenschlager R, Wakita T, Hijikata M, Shimotohno K. 

The Lipid droplet is an organelle important for Hepatitis C virus production.

Nature Cell Biology, 9.1089-1097. 2007. 

 

Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, and Shimotohno K.

CyclophilinB is a functional regulator of hepatitis C virus RNA polymerase. 

Molecular Cell. 19.111-122. 2005 

 

Murata T, Ohshima T, Yamaji M, Hosaka M, Miyanari Y, Hijikata M, Shimotohno K.

Suppression of hepatitis C virus replicon by TGF-beta. 

Virology. 331. 407-417. 2005 

 

Miyanari Y, Hijikata M, Yamaji M, Hosaka M, Takahashi H, and Shimotohno K. 

Hepatitis C virus Non-structural proteins in the probable membranous compartment function in viral genome replication. 

Journal of Biological Chemistry, 278,50301-50308, 2003 

 

Kishine H, Sugiyama K, Hijikata M, Kato N, Takahashi H, Noshi T, Nio Y, Hosaka M, Miyanari

Y, and Shimotohno K. 

Subgenomic replicon derived from a cell line infected with the hepatitis C virus. 

Biochemical and Biophysical Research Communications, 293, 993-999, 2002

 

Publications

Miyanari Y

TAL effector-mediated Genome Visualization (TGV)

Methods, 2014, Sep;69(2):198-204.

 

Miyanari Y*, Birling CZ. And Torres-Padilla ME*

Live visualization of chromatin dynamics using fluorescent TALEs

Nature Structural & Molecular Biology, 2013

*Corresponding authors    * Highlighted by Nature Methods

 

Li Y*, Miyanari Y*, Shirane K, Nitta H, Kubota T, Ohashi H, Okamoto A, Sasaki H.

Sequence-specific microscopic visualization of DNA methylation status at satellite repeats in individual cell nuclei and chromosomes

Nucleic Acids Research, 2013  *Equal contribution

 

Miyanari Y, Torres-Padilla ME. Control of ground-state pluripotency by allelic regulation of Nanog.     

Nature. 483.470-473. 2012

 

Miyanari Y, Torres-Padilla ME. 

Epigenetic regulation of reprogramming factors towards pluripotency in mouse preimplantation development. 

Curr Opin Endocrinol Diabetes Obes. 500-506.2010. Review

 

Hiura H, Sugawara A, Ogawa H, John RM, Miyauchi N, Miyanari Y, Horiike T, Li Y, Yaegashi N, Sasaki H, Kono T, Arima T. 

A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip. 

Nucleic Acids Res. 38:4929-45.2010.

 

Hishiki T, Shimizu Y, Tobita R, Sugiyama K, Ogawa K, Funami K, Ohsaki Y, Fuji moto T, Takaku H, Wakita T, Baumert TF, Miyanari Y, Shimotohno K. 

Infectivity of hepatitis C virusz is influenced by association with apolipoprotein E isoforms. 

J. Virol.84.12048-57. 2010. 

 

Ogawa K, Hishiki T, Shimizu Y, Funami K, Sugiyama K, Miyanari Y, Shimotohno K.

Hepatitis C virus utilizes lipid droplet for production of infectious virus.

Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(7):217-28. Review.

 

Miyanari Y, Atsuzawa K, Usuda N, Watashi K, Hishiki T, Zayas M, Bartenschlager R, Wakita T, Hijikata M, Shimotohno K. 

The Lipid droplet is an organelle important for Hepatitis C virus production.

Nature Cell Biology, 9.1089-1097. 2007. 

 

Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, and Shimotohno K.

CyclophilinB is a functional regulator of hepatitis C virus RNA polymerase. 

Molecular Cell. 19.111-122. 2005 

 

Murata T, Ohshima T, Yamaji M, Hosaka M, Miyanari Y, Hijikata M, Shimotohno K.

Suppression of hepatitis C virus replicon by TGF-beta. 

Virology. 331. 407-417. 2005 

 

Miyanari Y, Hijikata M, Yamaji M, Hosaka M, Takahashi H, and Shimotohno K. 

Hepatitis C virus Non-structural proteins in the probable membranous compartment function in viral genome replication. 

Journal of Biological Chemistry, 278,50301-50308, 2003 

 

Kishine H, Sugiyama K, Hijikata M, Kato N, Takahashi H, Noshi T, Nio Y, Hosaka M, Miyanari

Y, and Shimotohno K. 

Subgenomic replicon derived from a cell line infected with the hepatitis C virus. 

Biochemical and Biophysical Research Communications, 293, 993-999, 2002

 

Publications

Miyanari Y

TAL effector-mediated Genome Visualization (TGV)

Methods, 2014, Sep;69(2):198-204.

 

Miyanari Y*, Birling CZ. And Torres-Padilla ME*

Live visualization of chromatin dynamics using fluorescent TALEs

Nature Structural & Molecular Biology, 2013

*Corresponding authors    * Highlighted by Nature Methods

 

Li Y*, Miyanari Y*, Shirane K, Nitta H, Kubota T, Ohashi H, Okamoto A, Sasaki H.

Sequence-specific microscopic visualization of DNA methylation status at satellite repeats in individual cell nuclei and chromosomes

Nucleic Acids Research, 2013  *Equal contribution

 

Miyanari Y, Torres-Padilla ME. Control of ground-state pluripotency by allelic regulation of Nanog.     

Nature. 483.470-473. 2012

 

Miyanari Y, Torres-Padilla ME. 

Epigenetic regulation of reprogramming factors towards pluripotency in mouse preimplantation development. 

Curr Opin Endocrinol Diabetes Obes. 500-506.2010. Review

 

Hiura H, Sugawara A, Ogawa H, John RM, Miyauchi N, Miyanari Y, Horiike T, Li Y, Yaegashi N, Sasaki H, Kono T, Arima T. 

A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip. 

Nucleic Acids Res. 38:4929-45.2010.

 

Hishiki T, Shimizu Y, Tobita R, Sugiyama K, Ogawa K, Funami K, Ohsaki Y, Fuji moto T, Takaku H, Wakita T, Baumert TF, Miyanari Y, Shimotohno K. 

Infectivity of hepatitis C virusz is influenced by association with apolipoprotein E isoforms. 

J. Virol.84.12048-57. 2010. 

 

Ogawa K, Hishiki T, Shimizu Y, Funami K, Sugiyama K, Miyanari Y, Shimotohno K.

Hepatitis C virus utilizes lipid droplet for production of infectious virus.

Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(7):217-28. Review.

 

Miyanari Y, Atsuzawa K, Usuda N, Watashi K, Hishiki T, Zayas M, Bartenschlager R, Wakita T, Hijikata M, Shimotohno K. 

The Lipid droplet is an organelle important for Hepatitis C virus production.

Nature Cell Biology, 9.1089-1097. 2007. 

 

Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, and Shimotohno K.

CyclophilinB is a functional regulator of hepatitis C virus RNA polymerase. 

Molecular Cell. 19.111-122. 2005 

 

Murata T, Ohshima T, Yamaji M, Hosaka M, Miyanari Y, Hijikata M, Shimotohno K.

Suppression of hepatitis C virus replicon by TGF-beta. 

Virology. 331. 407-417. 2005 

 

Miyanari Y, Hijikata M, Yamaji M, Hosaka M, Takahashi H, and Shimotohno K. 

Hepatitis C virus Non-structural proteins in the probable membranous compartment function in viral genome replication. 

Journal of Biological Chemistry, 278,50301-50308, 2003 

 

Kishine H, Sugiyama K, Hijikata M, Kato N, Takahashi H, Noshi T, Nio Y, Hosaka M, Miyanari

Y, and Shimotohno K. 

Subgenomic replicon derived from a cell line infected with the hepatitis C virus. 

Biochemical and Biophysical Research Communications, 293, 993-999, 2002

 

Opportunities

We are seeking energetic and passionate postdocs and graduate students. We are very excited about uncovering molecular mechanisms underlyng cell-fate decision. If you are naturally curious about biology and enjoy working in a creative and dynamic environment, we would love to work with you!

 

We have an internship program for students to experience our lab for a few weeks. Traveling and accommodation fee will be supported by our institute.

 

If you are interested in a postdoc position, please send your application to miyanari<at>nibb.ac.jp with following attachments:

CV with a list of publications

a short summary of your achievements.

a short summary of your present and future research interests

a list of two references


Thank you for your interest!

 

Yusuke

Opportunities

We are seeking energetic and passionate postdocs and graduate students. We are very excited about uncovering molecular mechanisms underlyng cell-fate decision. If you are naturally curious about biology and enjoy working in a creative and dynamic environment, we would love to work with you!

We have an internship program for students to experience our lab for a few weeks. Traveling and accommodation fee will be supported by our institute.

If you are interested in a postdoc position, please send your application to miyanari<at>nibb.ac.jp with following attachments:
CV with a list of publications
a short summary of your achievements.
a short summary of your present and future research interests
a list of two references

Thank you for your interest!

Yusuke

Opportunities

 

We are seeking energetic and passionate postdocs and graduate students. We are very excited about uncovering molecular mechanisms underlyng cell-fate decision. If you are naturally curious about biology and enjoy working in a creative and dynamic environment, we would love to work with you!

 

We have an internship program for students to experience our lab for a few weeks. Traveling and accommodation fee will be supported by our institute.

 

If you are interested in a postdoc position, please send your application to miyanari<at>nibb.ac.jp with following attachments:

CV with a list of publications

a short summary of your achievements.

a short summary of your present and future research interests

a list of two references

 

Thank you for your interest!

 

Yusuke

 

Contact

 

Yusuke MIYANARI
Okazaki Institute for Integrative Bioscience
National Institute for Basic Biology
Division of Nuclear Dynamics
5-1 Higashiyama, Myodaijicho,

Okazaki 444-8787, JAPAN
Tel: +81  564 59 5850

Email: miyanari<at>nibb.ac.jp

 

ACCESS MAP

Yusuke MIYANARI

Okazaki Institute for Integrative Bioscience

National Institute for Basic Biology

Division of Nuclear Dynamics

5-1 Higashiyama, Myodaijicho,

Okazaki 444-8787, JAPAN

Tel: +81  564 59 5850

Email: miyanari<at>nibb.ac.jp

 

Contact

Yusuke MIYANARI

Okazaki Institute for Integrative Bioscience

National Institute for Basic Biology

Division of Nuclear Dynamics

5-1 Higashiyama, Myodaijicho,

Okazaki 444-8787, JAPAN

Tel: +81  564 59 5850

Email: miyanari<at>nibb.ac.jp