Molecular Genetic Analysis of Suppressor 2 of zeste Identifies Key Functional Domains

Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Genetics (Impact Factor: 5.96). 07/2009; 182(4):999-1013. DOI: 10.1534/genetics.108.097360
Source: PubMed


The Su(z)2 complex contains Posterior sex combs (Psc) and Suppressor 2 of zeste [Su(z)2], two paralogous genes that likely arose by gene duplication. Psc encodes a Polycomb group protein that functions as a central component of the PRC1 complex, which maintains transcriptional repression of a wide array of genes. Although much is known about Psc, very little is known about Su(z)2, the analysis of which has been hampered by a dearth of alleles. We have generated new alleles of Su(z)2 and analyzed them at the genetic and molecular levels. Some of these alleles display negative complementation in that they cause lethality when heterozygous with the gain-of-function Su(z)2(1) allele but are hemizygous and, in some cases, homozygous viable. Interestingly, alleles of this class identify protein domains within Su(z)2 that are highly conserved in Psc and the mammalian Bmi-1 and Mel-18 proteins. We also find several domains of intrinsic disorder in the C-terminal regions of both Psc and Su(z)2 and suggest that these domains may contribute to the essential functions of both proteins.

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    • "Together, these genetic analyses suggest that Su(z)2 is a strong suppressor of dE2f1-dsRNA phenotypes. We then sought to extend this observation by examining additional Su(z)2 alleles described recently (Emmons et al. 2009). "
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    • "). Natively unfolded regions occur in other chromatin architectural proteins, including the PcG proteins RYBP and GAGA factor, and have been proposed to play a role in the function of PSC and Su(z)2 (Agianian et al. 1999; Emmons et al. 2009; Lo et al. 2009; Neira et al. 2009). The linker histone regions required for chromatin compaction are intrinsically disordered in solution. "
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