Academic journal article Genetics

The Capacity to Act in Trans Varies among Drosophila Enhancers

Academic journal article Genetics

The Capacity to Act in Trans Varies among Drosophila Enhancers

Article excerpt

THE 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 specificpromotertarget(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 regulategeneexpressiontocommunicate 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 gene regulation called transvection (Lewis 1954). Evidence for enhancer action in trans has been uncovered at a handful of genes in the Drosophila genome, often providing an explanation for unexpected intragenic complementation of loss-of-function alleles (Lewis 1954; Gelbart 1982; Geyer et al. 1990; Leiserson et al. 1994; Hendrickson and Sakonju 1995; Casares et al. 1997; Morris et al. 1998; Southworth and Kennison 2002; Marin et al. 2004; Coulthard et al. 2005; Gohl et al. 2008; Juni and Yamamoto 2009), or the nonadditive activity of paired mutant and wild-type alleles (Gibson et al. 2000; Lum and Merritt 2011; Bing et al. 2014).

More recently, transgenic approaches based on site-specific recombination have been developed for Drosophila to query specific enhancer fragments and genomic positions for support of transvection (Chen et al. 2002; Kravchenko et al. 2005; Bateman et al. 2012a; Mellert and Truman 2012; also see Kassis et al. 1991). Thus far, transvection has been observed at all genomic insertion sites tested, suggesting that the Drosophila genome is generally permissive to enhancer action in trans. Furthermore, transgenic experiments have demonstrated that promoters at allelic positions in cis and trans to an enhancer will compete for the enhancer's activity, consistent with earlier classical observations (Geyer et al. 1990; Martinez-Laborda et al. 1992; Casares et al. 1997; Morris et al. 1999; Gohl et al. 2008). However, enhancer activation of promoters in cis and trans are not equivalent, with enhancers showing a strong preference for a promoter in cis, and frequently showing cell-to-cell variability in the activation of a promoter in trans (Bateman et al. 2012a; Mellert and Truman 2012).

Recently, Mellert and Truman (2012) used a transgenic approach to test 21 Drosophila enhancers for the capacity to support transvection. Their assay provided evidence that some, but not all, tested enhancers could activate a promoter on a paired homolog, raising the question of whether the capacity to act in trans is special to some enhancers. It does not appear that specific "tethering" sequences are required for an enhancer to act in trans since minimal enhancers consisting of multimerized binding sites for a single transcription factor can function in trans, even when that transcription factor is not native to Drosophila (Bateman et al. …

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