Academic journal article Genetics

Transvection Is Common throughout the Drosophila Genome

Academic journal article Genetics

Transvection Is Common throughout the Drosophila Genome

Article excerpt

ABSTRACT Higher-order genome organization plays an important role in transcriptional regulation. In Drosophila, somatic pairing of homologous chromosomes can lead to transvection, by which the regulatory region of a gene can influence transcription in trans. We observe transvection between transgenes inserted at commonly used phiC31 integration sites in the Drosophila genome. When two transgenes that carry endogenous regulatory elements driving the expression of either LexA or GAL4 are inserted at the same integration site and paired, the enhancer of one transgene can drive or repress expression of the paired transgene. These transvection effects depend on compatibility between regulatory elements and are often restricted to a subset of cell types within a given expression pattern. We further show that activated UAS transgenes can also drive transcription in trans. We discuss the implication of these findings for (1) understanding the molecular mechanisms that underlie transvection and (2) the design of experiments that utilize sitespecific integration.

THOUGH much of transcriptional regulation is due to regulatory elements that act in cis, relatively near the transcriptional start site of a gene, long-range and trans interactions can also affect gene regulation (reviewed in Henikoffand Comai 1998; Dekker 2008). To understand the prevalence and importance of these interactions, work has focused on higher-order genome organization, identifying which DNA sequence elements physically interact, and determining how these interactions affect transcription at the molecular level. One area where much progress has been made in understanding trans interactions is the study of transvection effects in Drosophila (reviewed in Duncan 2002; Kennison and Southworth 2002). Chromosomes are somatically paired in Diptera, so both copies of a gene are usually in proximity, even during interphase (Stevens 1908; Metz 1916; Csink and Henikoff1998; McKee 2004). In some cases, transvection occurs when the enhancer of one copy of a gene regulates expression of the paired copy of the gene in trans. Most examples of transvection were discovered as cases of intragenic complementation, in which two hypomorphic or loss-of-function alleles of a gene exhibit pairing-dependent complementation. Because of the low frequency of finding such complementary mutations, work on understanding transvection has focused on test cases including, but not limited to, the yellow (Geyer et al. 1990), Ultrabithorax (Lewis 1954), and white loci (Jack and Judd 1979; Gelbart and Wu 1982).

Despite the limited number of gene loci amenable to transvection studies, several important features of its underlying mechanism have been elucidated. For example, it has been established that enhancers of a gene more strongly activate transcription of the paired copy in trans if the cis core promoter is weakened or removed (Martínez-Laborda et al. 1992; Morris et al. 1999, 2004; Lee and Wu 2006; Gohl et al. 2008). Transvection may also be modified by zeste (Jack and Judd 1979), which has been found to be required for some examples of transvection (Kaufman et al. 1973; Gelbart and Wu 1982; Leiserson et al. 1994), and may facilitate physical interactions between alleles at some loci (Benson and Pirrotta 1988; Bickel and Pirrotta 1990). Finally, the genome appears to be generally permissive for transvection (Chen et al. 2002), so it is likely that many more genes undergo transvection than those that have been identified based on intragenic complementation.

The possible widespread nature of transvection presents a potential problem for transgene usage in Drosophila, specifically with regard to site-specific integration using the phiC31 integration system (Groth et al. 2004). Site-specific integration of transgenes is becoming increasingly common, as it provides the opportunity to control for and minimize genomic position effects (Markstein et al. 2008; Pfeiffer et al. 2010). …

Search by... Author
Show... All Results Primary Sources Peer-reviewed

Oops!

An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.