Visualization of Transvection in Living Drosophila Embryos

Abstract

How remote enhancers interact with appropriate target genes persists as a central mystery in gene regulation. Here, we exploit the properties of transvection to explore enhancer-promoter communication between homologous chromosomes in living Drosophila embryos. We successfully visualized the activation of an MS2-tagged reporter gene by a defined developmental enhancer located in trans on the other homolog. This trans-homolog activation depends on insulator DNAs, which increase the stability-but not the frequency-of homolog pairing. A pair of heterotypic insulators failed to mediate transvection, raising the possibility that insulator specificity underlies the formation of chromosomal loop domains. Moreover, we found that a shared enhancer co-activates separate PP7 and MS2 reporter genes incis and intrans. Transvecting alleles weakly compete with one another, raising the possibility that they share a common pool of the transcription machinery. We propose that transvecting alleles form a trans-homolog "hub," which serves as a scaffold for the accumulation of transcription complexes.

TADs pair homologous chromosomes to promote interchromosomal gene regulation

“…Using previously published ChIP-chip and ChIP-seq data , we found no association between pairing and any of the DNA-binding insulator proteins (BEAF, Su(Hw), CTCF, and GAF)( Fig. 4A-D), suggesting that complex combinations of bound insulators, rather than individual proteins, might contribute to homologous pairing or stabilize interactions between already paired TADs (Lim et al, 2018). Intriguingly, both Cp190 and Mod(mdg4), insulator co-factors that do not directly bind to DNA, were associated with pairing ( Fig.…”

BET inhibition disrupts transcription but retains enhancer-promoter contact

“…Enhancers can be situated far away from the genes they regulate 1,4 . Although not always the case 5,6 , at many gene loci proximity between enhancers and promoters is thought to be essential for enhancer function and gene activation 7,8 . How these enhancer-promoter interactions are initiated and maintained is not clearly understood.…”

Enhancer priming enables fast and sustained transcriptional responses to Notch signaling

“…One consequence of this is that factors modulating the levels of transcription can do so by changing either the frequency with which a burst occurs (measured by the gap between bursts) or the size of each burst (measured by changes in burst duration and/or amplitude). Since forced looping of the beta-globin enhancer to its promoter led to an increase in burst frequency (Bartman et al 2016), it has been proposed that transcription factors activate transcription by modulating enhancer-promoter interactions, and hence bursting frequency; although other studies suggest enhancer-promoter interactions are not the underlying basis of transcriptional bursting (Lim et al 2018;Chen et al 2018). Though the molecular origin of bursting remains unknown, bursting frequency rather than burst duration or amplitudes seems to be the major parameter modulated in different species and contexts (So et al 2011;Senecal et al 2014;Xu et al 2015;Desponds et al 2016;Padovan-Merhar et al 2015;Lammers et al 2018;Berrocal et al 2018).…”