Tunable Transcriptional Interference at the Endogenous Alcohol Dehydrogenase Gene Locus in Drosophila melanogaster

BioRxiv : the Preprint Server for Biology
Victoria JorgensenElçin Ünal

Abstract

Neighboring sequences of a gene can influence its expression. In the phenomenon known as transcriptional interference, transcription at one region in the genome can repress transcription at a nearby region in cis . Transcriptional interference occurs at a number of eukaryotic loci, including the alcohol dehydrogenase ( Adh ) gene in Drosophila melanogaster . Adh is regulated by two promoters, which are distinct in their developmental timing of activation. It has been shown using transgene insertion that when the promoter distal from the Adh start codon is deleted, transcription from the proximal promoter becomes de-regulated. As a result, the Adh proximal promoter, which is normally active only during the early larval stages, becomes abnormally activated in adults. Whether this type of regulation occurs in the endogenous Adh context, however, remains unclear. Here, we employed the CRISPR/Cas9 system to edit the endogenous Adh locus and found that removal of the distal promoter does also result in the untimely expression of the proximal promoter-driven mRNA isoform in adults, albeit at lower levels than previously reported. Importantly, we show that transcription from the distal promoter is sufficient to repress proximal transcr...Continue Reading

Related Concepts

Alcohol dehydrogenase
Chromatin
Drosophila
Drosophila melanogaster
Enzyme Repression
Genes
Genome
Histones
Larva
Transcription, Genetic

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