Two coacting shadow enhancers regulate twin of eyeless expression during early Drosophila development.

Autor:	Dresch JM; Biology Department, Clark University, 950 Main Street, Worcester, MA 01610, USA., Nourie LL; Biology Department, Clark University, 950 Main Street, Worcester, MA 01610, USA., Conrad RD; Biology Department, Clark University, 950 Main Street, Worcester, MA 01610, USA., Carlson LT; Biology Department, Clark University, 950 Main Street, Worcester, MA 01610, USA., Tchantouridze EI; Biology Department, Clark University, 950 Main Street, Worcester, MA 01610, USA., Tesfaye B; Biology Department, Clark University, 950 Main Street, Worcester, MA 01610, USA., Verhagen E; Biology Department, Clark University, 950 Main Street, Worcester, MA 01610, USA., Gupta M; Biology Department, Clark University, 950 Main Street, Worcester, MA 01610, USA., Borges-Rivera D; Biology Department, Clark University, 950 Main Street, Worcester, MA 01610, USA., Drewell RA; Biology Department, Clark University, 950 Main Street, Worcester, MA 01610, USA.
Jazyk:	angličtina
Zdroj:	Genetics [Genetics] 2024 Nov 28. Date of Electronic Publication: 2024 Nov 28.
DOI:	10.1093/genetics/iyae176
Abstrakt:	The Drosophila PAX6 homolog twin of eyeless (toy) sits at the pinnacle of the genetic pathway controlling eye development, the retinal determination network. Expression of toy in the embryo is first detectable at cellular blastoderm stage 5 in an anterior-dorsal band in the presumptive procephalic neuroectoderm, which gives rise to the primordia of the visual system and brain. Although several maternal and gap transcription factors that generate positional information in the embryo have been implicated in controlling toy, the regulation of toy expression in the early embryo is currently not well characterized. In this study, we adopt an integrated experimental approach utilizing bioinformatics, molecular genetic testing of putative enhancers in transgenic reporter gene assays and quantitative analysis of expression patterns in the early embryo, to identify 2 novel coacting enhancers at the toy gene. In addition, we apply mathematical modeling to dissect the regulatory landscape for toy. We demonstrate that relatively simple thermodynamic-based models, incorporating only 5 TF binding sites, can accurately predict gene expression from the 2 coacting enhancers and that the HUNCHBACK TF plays a critical regulatory role through a dual-modality function as an activator and repressor. Our analysis also reveals that the molecular architecture of the 2 enhancers is very different, indicating that the underlying regulatory logic they employ is distinct. Competing Interests: Conflicts of interest The authors report no competing interests. (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)
Databáze:	MEDLINE
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