The activity of < i > engrailed < /i > imaginal disc enhancers is modulated epigenetically by chromatin and autoregulation

by Yuzhong Cheng, Fountane Chan, Judith A. Kassisengrailed (en) encodes a homeodomain transcription factor crucial for the proper development of Drosophila embryos and adults. Like many developmental transcription factors,en expression is regulated by many enhancers, some of overlapping function, that drive expression in spatially and temporally restricted patterns. Theen embryonic enhancers are located in discrete DNA fragments that can function correctly in small reporter transgenes. In contrast, theen imaginal disc enhancers (IDEs) do not function correctly in small reporter transgenes. En is expressed in the posterior compartment of wing imaginal discs; in contrast, small IDE-reporter transgenes are expressed mainly in the anterior compartment. We found that En binds to the IDEs and suggest that it may directly repress IDE function and modulate En expression levels. We identified twoen IDEs, O and S. Deletion of either of these IDEs from a 79kb HA-en rescue transgene (HAen79) caused a loss-of-functionen phenotype when theHAen79 transgene was the sole source of En. In contrast, flies with a deletion of the same IDEs from an endogenousen gene had no phenotype, suggesting a resiliency not seen in theHAen79 rescue transgene. Inserting a gypsy insulator inHAen79 betweenen regulatory DNA and flanking sequences strengthened the activity ofHAen79, giving better function in both the ON and OFF transcriptional states. Altogether our data suggest that theen IDEs stimulate expression...

Source: PLoS Genetics - November 15, 2023 Category: Genetics & Stem Cells Authors: Yuzhong Cheng Source Type: research