Multimodal transcriptional control of pattern formation in embryonic development.

Autor:	Lammers NC; Biophysics Graduate Group, University of California, Berkeley, CA 94720., Galstyan V; Biochemistry and Molecular Biophysics Option, California Institute of Technology, Pasadena, CA 91126.; Department of Physics, Columbia University, New York, NY 10027., Reimer A; Biophysics Graduate Group, University of California, Berkeley, CA 94720., Medin SA; Department of Physics, University of California, Berkeley, CA 94720., Wiggins CH; Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY 10027; hggarcia@berkeley.edu chris.wiggins@columbia.edu.; Data Science Institute, Columbia University, New York, NY 10027.; Department of Systems Biology, Columbia University, New York, NY 10027.; Department of Statistics, Columbia University, New York, NY 10027., Garcia HG; Biophysics Graduate Group, University of California, Berkeley, CA 94720; hggarcia@berkeley.edu chris.wiggins@columbia.edu.; Department of Physics, University of California, Berkeley, CA 94720.; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.; Institute for Quantitative Biosciences-QB3, University of California, Berkeley, CA 94720.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Jan 14; Vol. 117 (2), pp. 836-847. Date of Electronic Publication: 2019 Dec 27.
DOI:	10.1073/pnas.1912500117
Abstrakt:	Predicting how interactions between transcription factors and regulatory DNA sequence dictate rates of transcription and, ultimately, drive developmental outcomes remains an open challenge in physical biology. Using stripe 2 of the even-skipped gene in Drosophila embryos as a case study, we dissect the regulatory forces underpinning a key step along the developmental decision-making cascade: the generation of cytoplasmic mRNA patterns via the control of transcription in individual cells. Using live imaging and computational approaches, we found that the transcriptional burst frequency is modulated across the stripe to control the mRNA production rate. However, we discovered that bursting alone cannot quantitatively recapitulate the formation of the stripe and that control of the window of time over which each nucleus transcribes even-skipped plays a critical role in stripe formation. Theoretical modeling revealed that these regulatory strategies (bursting and the time window) respond in different ways to input transcription factor concentrations, suggesting that the stripe is shaped by the interplay of 2 distinct underlying molecular processes. Competing Interests: The authors declare no competing interest. (Copyright © 2020 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
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