cis versus trans effects - senecio7の日記

Wittkopp PJ, Haerum BK & Clark AG 2008 Independent effects of cis- and trans-regulatory variation on gene expression in Drosophila melanogaster. Genetics 178:1831-1835.

over half of the yeast genes for which two quantitative trait loci (QTL) affecting gene expression were identified showed evidence of epistatic interactions (Brem et al. 2005)
specific interacting loci have not yet been identified
polymorphisms in cis-regulatory sequences and/or in genes encoding trans-acting factors may interact epistatically
such interactions could occur between two trans-acting loci, between two cis-acting loci, or between cis- and trans-acting loci
the relative importance of each type of interaction remains unknown
alternatively, interactions may occur at the molecular level without any sign of statistical (epistatic) interaction among polymorphisms at cis- and trans-acting loci

here, we show how the relative activity of two cis-regulatory alleles in different trans-regulatory backgrounds can be compared to test specifically for epistatic interactions between cis- and trans-acting polymorphisms
if cis- and trans-regulatory variants act independently, relative cis-regulatory activity should be the same in the two genetic backgrounds
if, however, cis- and trans-regulatory variants interact epistatically, relative cis-regulatory activity should differ between genetic backgrounds

relative allelic expression in a heterozygote is a measure of relative cis-regulatory activity (Cowles et al. 2002)

the absence of allele-specific, parent-of-origin effects is consistent with prior studies showing no evidence of genomic imprinting in D. melanogaster (Wittkopp et al. 2006)
more importantly, the similar allele-specific expression observed between the B and H classes indicates that genetic differences between the FM7 and In(1)AB X chromosomes had no effect on relative cis-regulatory activity
this was true for the three genes unaffected by the substitution of the X chromosome as well as for the five genes affected by trans-acting regulatory differences between the In(1)AB and FM7 X chromosomes, including the two genes with both cis- and trans-regulatory differences

this study shows how comparisons of allele-specific expression among genetic backgrounds can be used to test for epistasis between cis- and trans-regulatory variation
we started with a set of 22 autosomal genes
only 8 contained sequence differences suitable for pyrosequencing
only 2 showed the significant evidence of both cis- and trans-regulatory variation necessary to test for epistasis
neither of these genes showed evidence of epistatic interactions between cis- and trans-acting regulatory polymorphisms

prior studies suggest there may be extensive epistasis among loci underlying differential gene expression
interactions between cis- and trans-acting factors are only one source of these interactions

despite our small sample size, we propose that epistatic interactions between cis- and trans-acting factors may be rare in general
because they require trans-acting variants to interact differently with alternate cis-regulatory alleles
e.g., a polymorphism in the DNA binding region of a transcription factor may interact epistatically with a polymorphism in the cis-regulatory binding site for this factor
such combinations of polymorphisms may be rare within species

interactions among trans-regulatory polymorphisms may be more common
using a crossing design that minimized trans-regulatory variation, Hughes et al. (2006) found less evidence of epistasis among regulatory loci in Drosophila than did studies with other crossing designs

in the absence of interactions, cis- and trans-acting regulatory changes can evolve independently
cis-regulatory changes should have similar effects on gene expression, regardless of the genetic background

interactions between cis- and trans-acting changes have been implicated as a source of dysregulation in interspecific hybrids of D. melanogaster and D. simulans (Landry et al. 2005)