A view through a chromatin loop: insights into the ecdysone activation of early genes in Drosophila

Abstract

The early genes are a key group of ecdysone targets that function at the top of the signaling hierarchy. In the presence of ecdysone, early genes exhibit a highly characteristic rapid and powerful induction that represents a primary response. Multiple isoforms encoded by early genes then coordinate the activation of a larger group of late genes. While the general mechanism of ecdysone-dependent transcription is well characterized, it is not known whether a distinct mechanism governs the hormonal response of early genes. We previously found that one of the Drosophila early genes, E75, harbors multiple functional ecdysone response elements (EcREs). In this study we extended the analysis to Broad and E74 and found that EcRE multiplicity is a general feature of the early genes. Since most of the EcREs within early gene loci are situated distantly from promoters, we employed the chromosome conformation capture method to determine whether higher order chromatin structure facilitates hormonal activation. For each early gene we detected chromatin loops that juxtapose their promoters and multiple distant EcREs prior to ecdysone activation. Our findings suggest that higher order chromatin structure may serve as an important mechanism underlying the distinct response of early genes to ecdysone.

The Ecdysone Receptor Coactivator Taiman Links Yorkie to Transcriptional Control of Germline Stem Cell Factors in Somatic Tissue

“…Although the degree of Tai association with the ban-C12 region is relatively moderate, it is nonetheless equivalent to the degree of association of the Tai cofactor with the EcR-binding site in the Broad promoter ( EcB in Fig. S5J–K) (Bernardo et al, 2014), suggesting similar levels of Tai occupancy on each EcR-interaction site.…”

Combgap Promotes Ovarian Niche Development and Chromatin Association of EcR-Binding Regions in BR-C

“…The first viewpoint, B1 (at 1609904), was located between the distal and proximal promoters, 2 Kilo-Bases (KB) away from EcR binding sites. The second viewpoint (B2, at 1619647) was close to the proximal promoter, in a region within the first intron, which binds EcR in-vivo (S6 Fig) [35,36,37]. …”

“…In a similar vein, qPCR measurements show an order of magnitude difference in ecdysone induction levels between BR-C and DHR4 . Thus, induction strength is not determined in this case by the association per-se , but by individual promoters and/or the existence of other elements such as insulators, which participate in ecdysone-induced chromatin looping [35,40]. Whether Cg may participate in these complexes or even mediate some or their differences await biochemical analysis.…”

Complex cis-regulatory landscape of the insulin receptor gene underlies the broad expression of a central signaling regulator

“…For example, both InR and the Eip74EF/Eip75B genes are regulated by 20E and EcR (Gauhar et al, 2009;Bernardo et al, 2014). The InR gene contains elements that are either activated or repressed by 20E, whereas Eip74EF/Eip75B contain multiple copies of 20E activator elements.…”

“…Upon exposure to 20E, Eip74EF/Eip75B expression levels increase dramatically, whereas InR levels increase much more modestly (Fig. S13) (Bernardo et al, 2014;Mirth et al, 2014). The incoherent feed-forward properties of the InR gene, with simultaneous positive and negative effects, might ensure more precise changes in gene expression, preventing pleiotropic impacts Dashed lines indicate elements that are active in a cell type-specific manner.…”