The Differences Between Cis- and Trans-Gene Inactivation Caused by Heterochromatin in Drosophila.
Position-effect variegation (PEV) is the epigenetic disruption of gene expression near the de novo-formed euchromatin-heterochromatin border. Heterochromatic cis-inactivation may be accompanied by the trans-inactivation of genes on a normal homologous chromosome in trans-heterozygous combination with a PEV-inducing rearrangement. We characterize a new genetic system, inversion In(2)A4, demonstrating cis-acting PEV as well as trans-inactivation of the reporter transgenes on the homologous nonrearranged chromosome. The cis-effect of heterochromatin in the inversion results not only in repression but also in activation of genes, and it varies at different developmental stages. While cis-actions affect only a few juxtaposed genes, trans-inactivation is observed in a 500-kb region and demonstrates а nonuniform pattern of repression with intermingled regions where no transgene repression occurs. There is no repression around the histone gene cluster and in some other euchromatic sites. trans-Inactivation is accompanied by dragging of euchromatic regions into the heterochromatic compartment, but the histone gene cluster, located in the middle of the trans-inactivated region, was shown to be evicted from the heterochromatin. We demonstrate that trans-inactivation is followed by de novo HP1a accumulation in the affected transgene; trans-inactivation is specifically favored by the chromatin remodeler SAYP and prevented by Argonaute AGO2.
Department of Molecular Genetics of the Cell, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia.
Yuriy A
YA
Abramov
Department of Molecular Genetics of the Cell, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia.
Aleksei S
AS
Shatskikh
Institute of Gene Biology, Russian Academy of Sciences, Moscow 123182, Russia.
Oksana G
OG
Maksimenko
Department of Biology and Biotechnology "Charles Darwin," Sapienza University of Rome, 00185, Italy.
Silvia
S
Bonaccorsi
Department of Molecular Genetics of the Cell, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia gvozdev@img.ras.ru slavrov@img.ras.ru.
Vladimir A
VA
Gvozdev
Department of Molecular Genetics of the Cell, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia gvozdev@img.ras.ru slavrov@img.ras.ru.
Sergey A
SA
Lavrov
D000818:Animals; D000090266:Chromobox Protein Homolog 5; D055012:Chromosomal Position Effects; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D007446:Chromosome Inversion; D004330:Drosophila / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D017344:Genes, Insect; D017930:Genes, Reporter; D006570:Heterochromatin; D006657:Histones / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger; D019076:Transgenes
D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D012333:RNA, Messenger; D000090266:Chromobox Protein Homolog 5
Drosophila; PEV; heterochromatin; nuclear compartmentalization; trans-inactivation