Lola-I is a promoter pioneer factor that establishes de novo Pol II pausing during development

Vivekanandan Ramalingam, Xinyang Yu, Brian D. Slaughter, Jay R. Unruh, Kaelan J. Brennan, Anastasiia Onyshchenko, Jeffrey J. Lange, Malini Natarajan, Michael Buck and Julia Zeitlinger ()
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Vivekanandan Ramalingam: Stowers Institute for Medical Research
Xinyang Yu: State University of New York at Buffalo
Brian D. Slaughter: Stowers Institute for Medical Research
Jay R. Unruh: Stowers Institute for Medical Research
Kaelan J. Brennan: Stowers Institute for Medical Research
Anastasiia Onyshchenko: Stowers Institute for Medical Research
Jeffrey J. Lange: Stowers Institute for Medical Research
Malini Natarajan: Stowers Institute for Medical Research
Michael Buck: State University of New York at Buffalo
Julia Zeitlinger: Stowers Institute for Medical Research

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract While the accessibility of enhancers is dynamically regulated during development, promoters tend to be constitutively accessible and poised for activation by paused Pol II. By studying Lola-I, a Drosophila zinc finger transcription factor, we show here that the promoter state can also be subject to developmental regulation independently of gene activation. Lola-I is ubiquitously expressed at the end of embryogenesis and causes its target promoters to become accessible and acquire paused Pol II throughout the embryo. This promoter transition is required but not sufficient for tissue-specific target gene activation. Lola-I mediates this function by depleting promoter nucleosomes, similar to the action of pioneer factors at enhancers. These results uncover a level of regulation for promoters that is normally found at enhancers and reveal a mechanism for the de novo establishment of paused Pol II at promoters.

Date: 2023
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DOI: 10.1038/s41467-023-41408-1

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