Originally published as Genetics Published Articles Ahead of Print on September 15, 2006.

Genetics, Vol. 174, 1189-1204, November 2006, Copyright © 2006
doi:10.1534/genetics.106.057604

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

Christopher D. Shaffer^*,1, Giovanni Cenci, Brandi Thompson^*,, Gena E. Stephens^*, Elizabeth E. Slawson^*,, Kwame Adu-Wusu^*,**, Maurizio Gatti and Sarah C. R. Elgin^*

^* Department of Biology, Washington University, Saint Louis, Missouri 63130, Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università di Lecce, 73100 Lecce, Italy, Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan 48109, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, ^** Case School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 and Dipartimento di Genetica e Biologia Molecolare, Università di Roma La Sapienza, 00185 Rome, Italy

¹ Corresponding author: Department of Biology, CB-1229, Washington University, 1 Brookings Dr., St. Louis, MO 63130.
E-mail: shaffer{at}biology.wustl.edu

Drosophila melanogaster heterochromatin protein 2 (HP2) interacts with heterochromatin protein 1 (HP1). In polytene chromosomes, HP2 and HP1 colocalize at the chromocenter, telomeres, and the small fourth chromosome. We show here that HP2 is present in the arms as well as the centromeric regions of mitotic chromosomes. We also demonstrate that Su(var)2-HP2 exhibits a dosage-dependent modification of variegation of a yellow reporter transgene, indicating a structural role in heterochromatin formation. We have isolated and characterized 14 new mutations in the Su(var)2-HP2 gene. Using w^m4h, 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 (365 kDa) and HP2-S (175 kDa), 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.

This article has been cited by other articles:

				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. [Abstract] [Full Text] [PDF]

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