title: Differential gene silencing by trans-heterochromatin in Drosophila melanogaster.
abstract: The brown(Dominant) (bw(D)) allele contains a large insertion of heterochromatin leading to the trans-inactivation of the wild-type allele in bw(D)/bw(+) heterozygous flies. This silencing is correlated with the localization of bw(+) to a region of the interphase nucleus containing centric heterochromatin. We have used a series of transgene constructs inserted in the vicinity of the bw locus to demarcate both the extent of bw(D) influence along the chromosome and the relative sensitivities of various genes. Examples of regulatory regions that are highly sensitive, moderately sensitive, and insensitive were found. Additionally, by using the same transgene at increasing distances from the bw(D) insertion site in trans we were able to determine the range of influence of the heterochromatic neighborhood in terms of chromosomal distance. When the transgene was farther away from bw, there was, indeed, a tendency for it to be less trans-inactivated. However, insertion site also influenced silencing: a gene 86 kb away was trans-inactivated, while the same transgene 45 kb away was not. Thus location, distance, and gene-specific differences all influence susceptibility to trans-silencing near a heterochromatic neighborhood. These results have important implications for the ability of nuclear positioning to influence the expression of large blocks of a chromosome.
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA. csink@andrew.cmu.edu
authors.forename: Amy K
authors.initials: AK
authors.lastname: Csink
authors.forename: Alexander
authors.initials: A
authors.lastname: Bounoutas
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Griffith
authors.forename: Joy F
authors.initials: JF
authors.lastname: Sabl
authors.forename: Brian T
authors.initials: BT
authors.lastname: Sage
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D030801:Animals, Genetically Modified; D020169:Caspases; D004251:DNA Transposable Elements; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology; D005260:Female; D020868:Gene Silencing; D017344:Genes, Insect; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics; D006570:Heterochromatin / Q000502:physiology*; D019476:Insect Proteins / Q000235:genetics; D007763:Lac Operon; D008297:Male; D011401:Promoter Regions, Genetic; D019076:Transgenes
chemical_list: D018528:ATP-Binding Cassette Transporters; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006570:Heterochromatin; C087442:Hsp26 protein, Drosophila; D019476:Insect Proteins; C059253:bw protein, Drosophila; D020169:Caspases; C103568:Dcp-1 protein, Drosophila