Abstract
Suppressors and enhancers of position effect variegation (PEV) have been linked to the establishment and maintenance of heterochromatin. The presence of centromeres and other inheritance elements in heterochromatic regions suggests that suppressors and enhancers of PEV, Su(var) s and E(var)s [collectively termed Mod(var)s], may be required for chromosome inheritance. In order to test this hypothesis, we screened 59 ethyl methanesulfonate-generated Drosophila Mod(var)s for dominant effects on the partially compromised inheritance of a minichromosome (J21A) missing a portion of the genetically defined centromere. Nearly half of these Mod(var)s significantly increased or decreased the transmission of J21A. Analyses of homozygous mutant larval neuroblasts suggest that these mutations affect cell cycle progression and native chromosome morphology. Five out of six complementation groups tested displayed mitotic abnormalities, including phenotypes such as telomere fusions, overcondensed chromosomes, and low mitotic index. We conclude that Mod(var)s as a group are highly enriched for genes that encode essential inheritance functions. We propose that a primary function of Mod(var)s is to promote chromosome inheritance, and that the gene silencing phenotype associated with PEV may be a secondary consequence of the heterochromatic structures required to carry out these functions.
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Acknowledgements
We would like to thank Cameron Kennedy and Beth Sullivan for technical assistance, Barbara Wakimoto, Gunther Reuter, and Joel Eissenberg for Su(var) stocks used in the initial pilot screen and M. Blower, K. Hari, K. Maggert, B. Sullivan, R. Truelove, and C. Yan for critical comments. This work contributed to partial fulfillment of the requirements for a doctorate of philosophy in Biology at the University of California San Diego for K.D. and was funded by NIH R01 GM 54549 to G.H.K., and by NIH Institutional National Research Service Award CA-09370 and an American Cancer Society Postdoctoral Fellowship to K.R.C.
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Communicated by R. Allshire
H.D. Le and K.M. Donaldson contributed equally to this work
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Le, H.D., Donaldson, K.M., Cook, K.R. et al. A high proportion of genes involved in position effect variegation also affect chromosome inheritance. Chromosoma 112, 269–276 (2004). https://doi.org/10.1007/s00412-003-0272-2
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DOI: https://doi.org/10.1007/s00412-003-0272-2