Centers & Labs

RIKEN Center for Developmental Biology

Laboratory for Developmental Epigenetics

Team Leader: Ichiro Hiratani (Ph.D.)
Ichiro  Hiratani(Ph.D.)

We wish to clarify the molecular mechanisms underlying global facultative heterochromatin formation during early mouse embryogenesis, with the belief that understanding the developmental regulation of higher-order chromosome organization will lead to a deeper understanding of cell differentiation.

The term facultative heterochromatin refers to chromosomal regions that condense, become inactivated, and are stably maintained in this manner after a certain developmental stage. A classic example is the inactive X chromosome in mammals, which becomes detectable immediately prior to the formation of germ layers and is stably maintained thereafter in all downstream lineages. Intriguingly, we recently discovered that many autosomal domains also undergo a similar process of facultative heterochromatin formation at the same developmental stage, which accounts for more than 6% of the genome. This suggests that facultative heterochromatin formation at this stage is not specific to the inactive X, but rather a more widespread phenomenon affecting the entire genome. Recent studies have also revealed low reprogramming efficiency of cells immediately after this developmental stage, already as low as downstream somatic cell types. Thus, this facultative heterochromatin is a common epigenetic feature of all somatic cells beyond the germ layer formation stage, and the reprogramming experiments imply a potential link to the cell's differentiated state.

For these reasons, we combine genome-wide approaches with molecular and cell biology and imaging techniques to elucidate the molecular mechanisms underlying the facultative heterochromatin formation process. In the future, we will address the biological significance of this phenomenon and eventually wish to understand the fundamental implications of higher-order chromosome organization.

Main Research Field

Biology

Related Research Fields

Biological Sciences

Keywords

  • 3D genome organization
  • Epigenetics
  • DNA replication timing
  • Chromosomes
  • Embryonic stem cell differentiation

Selected Publications

  1. Shang W.H. et al.:
    "Chromosome engineering allows the efficient isolation of vertebrate neocentromeres."
    Dev Cell 24.635-48 (2013)
  2. Ryba T, et al.:
    "Genome-scale analysis of replication timing: from bench to bioinformatics."
    Nat Protoc 6.870-95 (2011)
  3. Hiratani I. and Gilbert D. M.:
    "Autosomal lyonization of replication domains during early Mammalian development."
    Adv Exp Med Biol 695.41-58 (2010)
  4. Ryba T, et al.:
    "Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types."
    Genome Res 20.761-70 (2010)
  5. Hiratani I, et al.:
    "Genome-wide dynamics of replication timing revealed by in vitro models of mouse embryogenesis."
    Genome Res 20.155-69 (2010)

Lab Members

Principal Investigator

Ichiro Hiratani
Team Leader

Core Members

Hisashi Miura
Research Scientist
Rawin Poonperm
Research Scientist
Asami Oji
Research Scientist
Saori Takahashi
Special Postdoctoral Researcher
Akie Tanigawa
Technical Staff I

Contact information

6F, RIKEN CDB Bldg.A, 2-2-3 Minatojima-minamimachi, Chuo-ku
Kobe, Hyogo
650-0047 Japan

Email: hiratani [at] cdb.riken.jp

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