Curr Biol.: auth.: group Vastenhouw

Curr Biol. 2023 Jan 9;33(1):164-173.e5. doi: 10.1016/j.cub.2022.11.015. Epub 2022 Dec 6.

Nanog organizes transcription bodies

Ksenia Kuznetsova 1Noémie M Chabot 2Martino Ugolini 2Edlyn Wu 2Manan Lalit 3Haruka Oda 4Yuko Sato 4Hiroshi Kimura 4Florian Jug 5Nadine L Vastenhouw 6

Abstract

The localization of transcriptional activity in specialized transcription bodies is a hallmark of gene expression in eukaryotic cells.13 How proteins of the transcriptional machinery come together to form such bodies, however, is unclear. Here, we take advantage of two large, isolated, and long-lived transcription bodies that reproducibly form during early zebrafish embryogenesis to characterize the dynamics of transcription body formation. Once formed, these transcription bodies are enriched for initiating and elongating RNA polymerase II, as well as the transcription factors Nanog and Sox19b. Analyzing the events leading up to transcription, we find that Nanog and Sox19b cluster prior to transcription. The clustering of transcription factors is sequential; Nanog clusters first, and this is required for the clustering of Sox19b and the initiation of transcription. Mutant analysis revealed that both the DNA-binding domain as well as one of the two intrinsically disordered regions of Nanog are required to organize the two bodies of transcriptional activity. Taken together, our data suggest that the clustering of transcription factors dictates the formation of transcription bodies.

Keywords: Nanog; RNA polymerase II; nuclear organization; transcription; transcription bodies; transcription factors; zebrafish.