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Kinetic principles underlying pioneer function of GAGA transcription factor in live cells

Xiaona Tang, Taibo Li, Sheng Liu, Jan Wisniewski, Qinsi Zheng, Yikang Rong, View ORCID ProfileLuke D. Lavis, Carl Wu
doi: https://doi.org/10.1101/2021.10.21.465351
Xiaona Tang
1Department of Biology, Johns Hopkins University, Baltimore, USA
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Taibo Li
1Department of Biology, Johns Hopkins University, Baltimore, USA
2Department of Biomedical Engineering, Johns Hopkins University, Baltimore, USA
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Sheng Liu
1Department of Biology, Johns Hopkins University, Baltimore, USA
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Jan Wisniewski
3Experimental Immunology Branch, National Cancer Institute, Bethesda, USA
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Qinsi Zheng
4Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
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Yikang Rong
5State Key Laboratory of Bio-control, Institute of Entomology, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
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Luke D. Lavis
4Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
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  • ORCID record for Luke D. Lavis
Carl Wu
1Department of Biology, Johns Hopkins University, Baltimore, USA
6Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, United States
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  • For correspondence: wuc{at}jhu.edu
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Abstract

How pioneer factors interface with chromatin to promote accessibility for transcription control is poorly understood in vivo. Here, we directly visualize chromatin association by the prototypical GAGA pioneer factor (GAF) in live Drosophila hemocytes. Single-particle tracking reveals that the majority of GAF is chromatin-bound, with a stable-binding fraction showing nucleosome-like confinement residing on chromatin for over 2 minutes, far longer than the dynamic range of most transcription factors. These kinetic properties require the full complement of GAF’s DNA-binding, multimerization and intrinsically disordered domains, and are autonomous from recruited chromatin remodelers NURF and PBAP, whose activities primarily benefit GAF’s neighbors such as HSF. Evaluation of GAF kinetics together with its endogenous abundance indicates that despite on-off dynamics, GAF constitutively and fully occupies chromatin targets, thereby providing a temporal mechanism that sustains open chromatin for transcriptional responses to homeostatic, environmental, and developmental signals.

Competing Interest Statement

L.D.L. and Q.Z. are listed as inventors on patents and patent applications whose values might be affected by publication.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 07, 2022.
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Kinetic principles underlying pioneer function of GAGA transcription factor in live cells
Xiaona Tang, Taibo Li, Sheng Liu, Jan Wisniewski, Qinsi Zheng, Yikang Rong, Luke D. Lavis, Carl Wu
bioRxiv 2021.10.21.465351; doi: https://doi.org/10.1101/2021.10.21.465351
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Kinetic principles underlying pioneer function of GAGA transcription factor in live cells
Xiaona Tang, Taibo Li, Sheng Liu, Jan Wisniewski, Qinsi Zheng, Yikang Rong, Luke D. Lavis, Carl Wu
bioRxiv 2021.10.21.465351; doi: https://doi.org/10.1101/2021.10.21.465351

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