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 spatial and temporal dynamics of gene expression in development. Through interaction with sequence-specific transcription factors and co-activators, enhancers modulate when and where genes should be transcribed in response to intringic and extrinsic signals. Recent whole-genome studies estimated that the human genome contains approximately 900,000 enhancers, suggesting that a typical human gene is regulated by 〜40-50 enhancers. Mutation in enhancers can cause dysregulation of transcriptional program, which in turn leads to human diseases such as cancer. Growing number of evidences suggest that diversification of enhancer function is a major source of phenotypic polymorphism among population. While enhancer’s biological importance is becoming increasingly clear in recent years, very little is known about the basic mechanism of enhancer function in the control of gene expression. Especially, the nature of enhancer-promoter communication and its dynamics remain as an outstanding mystery in genome biology. By using a wide-range of experimental approaches such as live-imaging, genome-editing, super-resolution microscopy and whole-genome sequencing methods, 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 dynamics of transcriptional regiulation by enhances in early Drosophila embryos. By combining this unique experimental approach with cutting-edge technologies such as genome-editing and super-resolution microspcopy, we aim to understand the dynamic nature of enhancer-promoter communication in animal development.

Pressrelease

Unveiling the roles of non-coding enhancer transcription in living Drosophila embryos
Regulation of transcriptional bursting by core promoter elements
How do embryos establish reproducible spatial patterns of gene expression from stochastic transcription?

Publication

  1. Dynamic modulation of enhancer responsiveness by core promoter elements in living Drosophila embryos.
    Yokoshi M, Kawasaki K (co-first), Cambón M, Fukaya T.
    Nucleic Acids Research. 50(1):92-107.
  2. Dynamic regulation of anterior-posterior patterning genes in living Drosophila embryos.
    Fukaya T.
    Current Biology. 31(10):2227-2236.
  3. Tissue-scale mechanical coupling reduces morphogenetic noise to ensure precision during epithelial folding
    Eritano A.S, Bromley C.L, Bolea Albero A, Schütz L, Wen F.-L, Takeda M, Fukaya T, Sami M.M, Shibata T, Lemke S, and Wang Y.-C.
    Developmental Cell. 53(2):212-228.
  4. Visualizing the role of boundary elements in enhancer-promoter communication.
    Yokoshi M, Segawa K, Fukaya T.
    Molecular Cell. 78(2):224-235.
  5. Large distances separate co-regulated genes in living Drosophila embryos
    Heist T, Fukaya T, Levine M.
    Proc. Natl. Acad. Sci. USA. 116(30):15062-15067.
  6. 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
  7. Visualization of transvection in living Drosophila embryos
    Lim B, Heist T, Levine M, Fukaya T.
    Molecular Cell. 70 (2), 287-296.
  8. Transvection
    Fukaya T, Levine M
    Current Biology. 27 (19), R1047-R1049, 2017
  9. Rapid rates of Pol II elongation in the Drosophila embryo.
    Fukaya T, Lim B, Levine M
    Current Biology. 27 (9), 1387–1391, 2017
  10. Enhancer control of transcriptional bursting.
    Fukaya T, Lim B, Levine M
    Cell. 166 (2), 358–368, 2016
Takashi FUKAYA
Associate Professor
Ph.D.
Graduate School of Arts and Sciences
Shiho Makino
Research Associate
Ph.D.