From promoter motif to cardiac function: a single DPE motif affects transcription regulation and organ function in vivo

Sloutskin A, Itzhak D, Vogler G, Pozeilov H, Ideses D, Alter H, Adato O, Shachar H, Doniger T, Shohat-Ophir G, Frasch M, Bodmer R, Duttke SH, Juven-Gershon T (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Development Company of Biologists

Book Volume: 151

Journal Issue: 14

DOI: 10.1242/dev.202355

Abstract

Transcription initiates at the core promoter, which contains distinct core promoter elements. Here, we highlight the complexity of transcriptional regulation by outlining the effect of core promoter-dependent regulation on embryonic development and the proper function of an organism. We demonstrate in vivo the importance of the downstream core promoter element (DPE) in complex heart formation in Drosophila. Pioneering a novel approach using both CRISPR and nascent transcriptomics, we show the effects of mutating a single core promoter element within the natural context. Specifically, we targeted the downstream core promoter element (DPE) of the endogenous tin gene, encoding the Tinman transcription factor, a homologue of human NKX2-5 associated with congenital heart diseases. The 7 bp substitution mutation results in massive perturbation of the Tinman regulatory network that orchestrates dorsal musculature, which is manifested as physiological and anatomical changes in the cardiac system, impaired specific activity features, and significantly compromised viability of adult flies. Thus, a single motif can have a critical impact on embryogenesis and, in the case of DPE, functional heart formation.

Authors with CRIS profile

Manfred Frasch Lehrstuhl für Entwicklungsbiologie

Involved external institutions

Sanford Burnham Prebys Medical Discovery Institute US United States (USA) (US) Bar-Ilan University IL Israel (IL) Washington State University (WSU) US United States (USA) (US)

How to cite

APA:

Sloutskin, A., Itzhak, D., Vogler, G., Pozeilov, H., Ideses, D., Alter, H.,... Juven-Gershon, T. (2024). From promoter motif to cardiac function: a single DPE motif affects transcription regulation and organ function in vivo. Development, 151(14). https://doi.org/10.1242/dev.202355

MLA:

Sloutskin, Anna, et al. "From promoter motif to cardiac function: a single DPE motif affects transcription regulation and organ function in vivo." Development 151.14 (2024).

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