Genetics. Published Articles Ahead of Print: September 15, 2006, Copyright © 2006
doi:10.1534/genetics.106.057604


A more recent version of this article appeared on November 1, 2006.


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The Large Isoform of Drosophila melanogaster Heterochromatin Protein 2 Plays a Critical Role in Gene Silencing and Chromosome Structure

1 Washington University in St. Louis
2 Università di Lecce
3 University of Michigan
4 University of California, Berkeley
5 Case Western Reserve University
6 Università di Roma La Sapienza

* To whom correspondence should be addressed. E-mail: chris{at}biology.wustl.edu.

Submitted on February 28, 2006
Revised on May 16, 2006
Accepted on 31 August 2006


Abstract

Drosophila melanogaster Heterochromatin Protein 2 (HP2) interacts with Heterochromatin Protein 1 (HP1). In polytene chromosomes, HP2 and HP1 co-localize at the chromocenter, telomeres, and the small fourth chromosome. We now show that HP2 is present in the arms as well as the centromeric regions of mitotic chromosomes. We also demonstrate that Su(var)2- HP2exhibits a dosage-dependent modification of variegation of a yellow reporter transgene, indicating a structural role in heterochromatin formation. We have isolated and characterized fourteen new mutations in the Su(var)2-HP2 gene. Using wm4h, many (but not all) mutant alleles show dominant Su(var) activity. Su(var)2-HP2 mutant larvae show a wide variety of mitotic abnormalities, but not the telomere fusion seen in larvae deficient for HP1. The Su(var)2- HP2 gene codes for two isoforms; HP2-L, (ca. 365 kD), and HP2-S (ca. 175 kD), lacking exons 5 and 6. In general, mutations that affect only the larger isoform result in more pronounced defects than do mutations common to both isoforms. This suggests that an imbalance between large and small isoforms is particularly deleterious. These results indicate a role for HP2 in the structural organization of chromosomes and in heterochromatin-induced gene silencing and show that the larger isoform plays a critical role in these processes.

Key Words: D. melanogaster, HP2, chromosome morphology, gene silencing, heterochromatin




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K. A. Haynes, E. Gracheva, and S. C. R. Elgin
A Distinct Type of Heterochromatin Within Drosophila melanogaster Chromosome 4
Genetics, March 1, 2007; 175(3): 1539 - 1542.
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