Enhancer Choice in Cis and in Trans in Drosophila melanogaster

Morris, James R.; Petrov, Dmitri A.; Lee, Anne M.; Wu, Chao-ting

doi:10.1534/genetics.104.026955

Cited by 38 publications

(57 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given the wide range of transvection strength observed in our study, our data suggest that such combined action of enhancers in cis and trans may be more relevant to some genes than others. Consistent with this, enhancer action in trans observed using classical alleles of different genes can produce widely varying levels of transcription, from 1% or less of wild-type levels using certain alleles of yellow (Morris et al 2004), to near 100% of wild-type activity for some alleles of the Men and snGlycerol-3-Phosphate Dehydrogenase genes (Gibson et al 1999;Lum and Merritt 2011). In addition, many other types of regulatory sequences, including insulators and Polycomb response elements, may function more efficiently when paired or clustered (reviewed by Bantignies and Cavalli 2011;Herold et al 2012).…”

Section: Does Transvection Play a Role In The Wild?supporting

confidence: 53%

The Capacity to Act in Trans Varies Among Drosophila Enhancers

Blick

Mayer-Hirshfeld

Malibiran³

et al. 2016

Genetics

View full text Add to dashboard Cite

The interphase nucleus is organized such that genomic segments interact in cis, on the same chromosome, and in trans, between different chromosomes. In Drosophila and other Dipterans, extensive interactions are observed between homologous chromosomes, which can permit enhancers and promoters to communicate in trans. Enhancer action in trans has been observed for a handful of genes in Drosophila, but it is as yet unclear whether this is a general property of all enhancers or specific to a few. Here, we test a collection of well-characterized enhancers for the capacity to act in trans. Specifically, we tested 18 enhancers that are active in either the eye or wing disc of third instar Drosophila larvae and, using two different assays, found evidence that each enhancer can act in trans. However, the degree to which trans-action was supported varied greatly between enhancers. Quantitative analysis of enhancer activity supports a model wherein an enhancer's strength of transcriptional activation is a major determinant of its ability to act in trans, but that additional factors may also contribute to an enhancer's trans-activity. In sum, our data suggest that a capacity to activate a promoter on a paired chromosome is common among Drosophila enhancers.KEYWORDS RMCE; interchromosomal interactions; long-range enhancer; somatic homolog pairing; transvection T HE spatial organization of the interphase eukaryotic genome is characterized by extensive long-distance interactions between distal chromosome regions (Sanyal et al. 2012). Interactions have been identified between sequences on the same chromosome (in cis) or on different chromosomes (in trans) (Lieberman-Aiden et al. 2009;Duan et al. 2010;Sexton et al. 2012;van de Werken et al. 2012;Nagano et al. 2013;Zhang et al. 2013). Many long-distance interactions in cis underlie the activation of specific genes, and in some cases, sequences have been identified that facilitate interactions between a distal enhancer and a specific promoter target (Zhou and Levine 1999;Calhoun et al. 2002;Calhoun and Levine 2003;Lin 2003;Akbari et al. 2008;Fujioka et al. 2009;Majumder et al. 2015). In contrast, the genetic impacts of trans-interactions between chromosomes are less clearly understood. Examples of gene regulation involving interchromosomal associations have been described (Spilianakis et al. 2005;Bacher et al. 2006;Xu et al. 2006;Apostolou and Thanos 2008;Sandhu et al. 2009;Markenscoff-Papadimitriou et al. 2014;Patel et al. 2014), but it remains unclear whether it is common for sequences that regulate gene expression to communicate between different chromosomes when they are physically juxtaposed.In Drosophila melanogaster, extensive trans-interactions are observed between homologous chromosomes in virtually all somatic tissues, a phenomenon known as somatic homolog pairing (reviewed by McKee 2004;Bosco 2012). The close proximity of homologous chromosomes in Drosophila can permit an enhancer to act in trans on a promoter on the paired homolog, a form of pairing-dependent ...

show abstract

Section: Does Transvection Play a Role In The Wild?supporting

confidence: 53%

The Capacity to Act in Trans Varies Among Drosophila Enhancers

Blick

Mayer-Hirshfeld

Malibiran³

et al. 2016

Genetics

View full text Add to dashboard Cite

show abstract

“…However, our results may be consistent with existing data from the yellow locus. Here, promoter mutations show that full phenotypic complementation can be achieved with 11% of wild-type levels of yellow transcript generated in cis, implying that enhancer action in trans, which shows only partial complementation, contributes an even lower amount of transcript (Morris et al 2004). In contrast, quantitative analyses of transvection at the genes encoding Gpdh and Men suggest that their enhancers can contribute up to 100% of normal cis-activity via enhancer action in trans, but that strength of trans-activity varies greatly with allele structure (Gibson et al 1999;Lum and Merritt 2011).…”

Section: Discussionmentioning

confidence: 89%

Comparing Enhancer Action in Cis and in Trans

2012

View full text Add to dashboard Cite

Studies from diverse systems have shown that distinct interchromosomal interactions are a central component of nuclear organization. In some cases, these interactions allow an enhancer to act in trans, modulating the expression of a gene encoded on a separate chromosome held in close proximity. Despite recent advances in uncovering such phenomena, our understanding of how a regulatory element acts on another chromosome remains incomplete. Here, we describe a transgenic approach to better understand enhancer action in trans in Drosophila melanogaster. Using phiC31-based recombinase-mediated cassette exchange (RMCE), we placed transgenes carrying combinations of the simple enhancer GMR, a minimal promoter, and different fluorescent reporters at equivalent positions on homologous chromosomes so that they would pair via the endogenous somatic pairing machinery of Drosophila. Our data demonstrate that the enhancer GMR is capable of activating a promoter in trans and does so in a variegated pattern, suggesting stochastic interactions between the enhancer and the promoter when they are carried on separate chromosomes. Furthermore, we quantitatively assessed the impact of two concurrent promoter targets in cis and in trans to GMR, demonstrating that each promoter is capable of competing for the enhancer's activity, with the presence of one negatively affecting expression from the other. Finally, the single-cell resolution afforded by our approach allowed us to show that promoters in cis and in trans to GMR can both be activated in the same nucleus, implying that a single enhancer can share its activity between multiple promoter targets carried on separate chromosomes.

show abstract

“…Specific genomic regions have been shown to modulate transvection at other loci. At the yellow locus, for example, specific wing and body enhancer elements are capable of acting in trans to drive gene expression (Morris et al 1998(Morris et al , 2004. These examples are dependent on the alleles being cis-promoter deficient, and our genomic analysis suggests that the MenExi 2 alleles are similarly promoter deficient (Figure 4).…”

mentioning

confidence: 73%

“…At paired loci, enhancer elements have been shown to act on a trans-promoter when its cis-promoter is deficient, increasing overall gene expression (Geyer et al 1990;Morris et al 1998Morris et al , 1999Morris et al , 2004Lee and Wu 2006). In the specific case of the Men locus, and MEN enzyme activity, we expect that excision/wild-type heterozygotes would have 50% wild-type activity if the MenExi 2 allele contributed no activity.…”

Section: P-element Excision-derived Men Allelesmentioning

confidence: 97%

Nonclassical Regulation of Transcription: Interchromosomal Interactions at the Malic enzyme Locus of Drosophila melanogaster

Lum

Merritt

2011

Genetics

View full text Add to dashboard Cite

Regulation of transcription can be a complex process in which many cis-and trans-interactions determine the final pattern of expression. Among these interactions are trans-interactions mediated by the pairing of homologous chromosomes. These transeffects are wide ranging, affecting gene regulation in many species and creating complex possibilities in gene regulation. Here we describe a novel case of trans-interaction between alleles of the Malic enzyme (Men) locus in Drosophila melanogaster that results in allele-specific, non-additive gene expression. Using both empirical biochemical and predictive bioinformatic approaches, we show that the regulatory elements of one allele are capable of interacting in trans with, and modifying the expression of, the second allele. Furthermore, we show that nonlocal factors-different genetic backgrounds-are capable of significant interactions with individual Men alleles, suggesting that these trans-effects can be modified by both locally and distantly acting elements. In sum, these results emphasize the complexity of gene regulation and the need to understand both small-and large-scale interactions as more complete models of the role of trans-interactions in gene regulation are developed.T HE regulation of gene expression is a complex process often involving many levels of organization. In a simple model, gene expression is determined by intragenic interactions (e.g., enhancer-promoter interactions occurring in cis on the same chromosome). In more complex models of regulation, expression is also influenced by the threedimensional genomic structure and organization of chromosomes. In the latter, more realistic models, nuclear organization governs interactions between neighboring genetic elements, such as transcription factories, heterochromatin, homologous chromosomes, and genes that are capable of acting in trans to modulate gene expression (reviewed in Henikoff and Comai 1998;Wu and Morris 1999;Lanctot et al. 2007;Xu and Cook 2008). These transinteractions create levels of complexity in gene regulation involving interphase chromatin structuring, its impact on pairing of homologs, and the potential exchange of transcriptional or regulatory proteins between homologs. One such trans-interaction, transvection, is the modification of gene activity through interactions between the regulatory elements of one allele and its homolog on the homologous chromosome (reviewed by Pirrotta 1999;Wu and Morris 1999;Duncan 2002). Here we describe a case of trans-interaction at the Malic enzyme locus (Men) (Merritt et al. 2005), potentially transvection, and examine interactions between putative regulatory elements on homologous chromosomes.The term "transvection" was first coined by E. B. Lewis (1954) to describe complementation and trans-interactions between two Ultrabithorax (Ubx) alleles in Drosophila. Lewis found that certain Ubx alleles were able to complement each other and that this complementation could be interrupted by chromosomal rearrangements that disrupted local homolog p...

show abstract

Enhancer Choice in Cis and in Trans in Drosophila melanogaster

Cited by 38 publications

References 42 publications

The Capacity to Act in Trans Varies Among Drosophila Enhancers

The Capacity to Act in Trans Varies Among Drosophila Enhancers

Comparing Enhancer Action in Cis and in Trans

Nonclassical Regulation of Transcription: Interchromosomal Interactions at the Malic enzyme Locus of Drosophila melanogaster

Contact Info

Product

Resources

About