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

• Published in: Nature communications Vol. 14; no. 1; pp. 5862 - 14
• Main Authors: Ramalingam, Vivekanandan, Yu, Xinyang, Slaughter, Brian D., Unruh, Jay R., Brennan, Kaelan J., Onyshchenko, Anastasiia, Lange, Jeffrey J., Natarajan, Malini, Buck, Michael, Zeitlinger, Julia
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.09.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 14/32; 45/23; 49/15; 49/88; 49/90; 49/91; 631/208/200; 631/208/212; 64/24; 82/29; 82/51; Accessibility; Animals; DNA-directed RNA polymerase; Drosophila - genetics; Embryo, Mammalian; Embryogenesis; Embryonic Development; Embryonic growth stage; Enhancers; Gene expression; Humanities and Social Sciences; multidisciplinary; Nucleosomes; Nucleosomes - genetics; Promoter Regions, Genetic - genetics; Promoters; RNA polymerase; RNA polymerase II; RNA Polymerase II - genetics; Science; Science (multidisciplinary); Zinc finger proteins
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-41408-1

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. Gene promoters are very often poised for expression by paused RNA polymerase II. Here, Ramalingam et al., identify a mechanism for the de novo establishment of paused Pol II at promoters and study its effects on expression.