Nucleolus organizer-suppressed position-effect variegation inDrosophila melanogaster

Abstract

The white locus is inactivated in a cell-by-cell variegated pattern when juxtaposed with the proximal or distal parts of the nucleolus organizer region (NO) by X chromosome inversion. Recombinants for two such inversions, w m5lb and w m4 , were obtained and randomized for genetic background. White locus activity was much higher in the w m4 recombinant duplicated for most of the NO and much lower in the w m5lb recombinant deficient for it. Although there may be other molecular differences between the heterochromatic regions of the recombinants, the most obvious is the dosage of NO. Suppression of a NO region-evoked variegated phenotype by additional NO doses is discussed in relation to four different classes of models for position-effect variegation (PEV): chromatin structure, nuclear geometry, incomplete transposition of mobile elements, and heterochromatin promoter-driven transcription. A corollary of the structural model is functional subdivision of heterochromatin, which would enable the use of PEV as a tool for its study.

Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes

“…This may be analogous to previous observations in Drosophila in which deletion or amplification of rDNA or satellite DNA repeats enhance or suppress position effect variegation by varying the amount of the modifier proteins that are bound (33,34). Polymorphic variation in the numbers of such repeats would provide a plausible explanation for the clinical variability seen in patients with identical mutations of the ATRX gene producing a structurally normal but reduced amount of ATRX (3,35).…”

Ribosomal DNA contributes to global chromatin regulation

“…Others have noted the opposite effectincreased silencing with decreased X-linked rDNA arrays of males (27,28). Whether the X-linked and Y-linked arrays are fundamentally different remains a question, although there are clear differences in sequence and epigenetic regulation of these arrays (20,24).…”

“…The rDNA and nucleolus have played a prominent role in evolving theories of aging, metabolism, cell differentiation, cell cycle control, cancer progression, and gene regulation (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The rDNA is of particular interest in understanding heterochromatin because it is known to be regulated by epigenetic modification (20)(21)(22)(23)(24), is associated with both active and repressive protein modification (25,26), can affect variegation at unlinked genes (27,28), can itself induce variegation (29)(30)(31), and may change its size and regulation through the lifespan of an organism (32,33). Few studies, however, have probed the connection between the rDNA, nucleolus, and heterochromatin formation in the nucleus.…”

Expression of I-CreI Endonuclease Generates Deletions Within the rDNA of Drosophila

“…Even chromosomes isolated from a common stock may differ twofold in rDNA content (Averbeck and Eickbush 2005). Although not mapped to the rDNA, chromosome polymorphisms can have considerable effects on gene activity (Spofford and Desalle 1991;Lemos et al 2008).…”

“…Hypotheses that rDNA quantity is tied to aging, disease, or gene regulation exist but are difficult to test without some way to manipulate the rDNA array size (Spofford and Desalle 1991;Gotta et al 1997;Palumbo et al 1994;Johnson et al 1999;Weber et al 1999;Carmo-Fonseca et al 2000;Martindill et al 2007;Versa-Ostojć et al 2008). Only by altering the initial size of the rDNA array, in an otherwise isogenic background, can the contribution of rDNA size to these pleiotropic phenomena be investigated.…”