Theme

Our lab uses quantitative live imaging methods to investigate how cis -regulatory DNA elements control transcription dynamics in development.

About Research

Visualizing enhancer dynamics in living embryos

Enhancers are regulatory DNAs that control spatiotemporal patterning of gene expression in development. By integrating information from sequence specific transcription factors and co-activators, enhancers precisely regulate when and where genes should be transcribed. Recent whole genome studies estimated that the human genome contains approximately 400,000 enhancers, suggesting that a typical human gene is regulated by 〜20 enhancers. Mutation in enhancers often causes dysregulation of transcriptional program, which can lead to human diseases such as cancer. It has also been reported that diversification of enhancer function is a major source of phenotypic polymorphism among population. However, while their biological importance is becoming increasingly clear in recent years, very little is known about the basic mechanism of enhancer function. Especially, the nature of enhancer-promoter communication and its dynamics remain as an outstanding mystery since the first discover of prototypic SV40 enhancer more than 35 years ago. By combining wide-range of experimental approaches including live-imaging, genome editing, biochemistry and optogenetics, we aim to elucidate fundamentally new dimension of the molecular mechanism underlying transcriptional control in development.

Our lab uses quantitative live imaging method to visualize spatiotemporal dynamics of enhancer action in developing Drosophila embryos. By combining this unique experimental approach with cutting-edge technologies such as genome editing and optogenetics, we aim to obtain comprehensive understanding of how enhancers control transcriptional dynamics in development.

Publication

  1. Temporal dynamics of pair-rule stripes in living Drosophila embryos
    Lim B, Fukaya T, Heist T, Levine M.
    Proc. Natl. Acad. Sci. USA. 115(33):8376-8381
  2. Visualization of transvection in living Drosophila embryos
    Lim B, Heist T, Levine M, Fukaya T.
    Molecular Cell. 70 (2), 287-296.
  3. Transvection
    Fukaya T, Levine M
    Current Biology. 27 (19), R1047-R1049, 2017
  4. Rapid rates of Pol II elongation in the Drosophila embryo.
    Fukaya T, Lim B, Levine M
    Current Biology. 27 (9), 1387–1391, 2017
  5. Enhancer control of transcriptional bursting.
    Fukaya T, Lim B, Levine M
    Cell. 166 (2), 358–368, 2016
  6. CCR4 and CAF1 deadenylases have an intrinsic activity to remove the post-poly(A) sequence.
    Niinuma S, Fukaya T, Tomari Y
    RNA. 22 (10), 1550-1559, 2016
  7. MicroRNAs block assembly of eIF4F initiation complex in Drosophila.
    Fukaya T, Iwakawa HO, Tomari Y
    Molecular Cell. 28;48(6):825-36, 2014
  8. MicroRNAs mediate gene silencing via multiple different silencing pathways in Drosophila.
    Fukaya T, Tomari Y
    Molecular Cell. 28;48(6):825-36, 2012
  9. RNA processing bodies, peroxisomes, Golgi bodies, mitochondria, and endoplasmic reticulum tubule junctions frequently pause at cortical microtubules.
    Hamada T, Tominaga M, Fukaya T, Nakamura M, Nakano A, Watanabe Y, Hashimoto T, Baskin TI.
    Plant and Cell Physiology. 53(4):699-708, 2012
  10. PABP is not essential for microRNA-mediated translational repression and deadenylation in vitro.
    Fukaya T, Tomari Y.
    The EMBO Journal. 30(24):4998-5009, 2011
Takashi FUKAYA
Lecturer
Ph.D.
Graduate School of Arts and Sciences
Moe Yokoshi
Research Associate
Ph.D.