Abstract
Yeast SIR2 is a NAD+-dependent histone deacetylase required for heterochromatic silencing at telomeres, rDNA, and mating-type loci. We find that the Drosophila homolog of Sir2 (dSir2) also encodes deacetylase activity and is required for heterochromatic silencing, but unlike ySir2, is not required for silencing at telomeres. We show that dSir2 interacts genetically and physically with members of the Hairy/Deadpan/E(Spl) family of bHLH euchromatic repressors, key regulators of Drosophila development. dSir2 is an essential gene whose loss of function results in both segmentation defects and skewed sex ratios, associated with reduced activities of the Hairy and Deadpan bHLH repressors. These results indicate that Sir2 in higher organisms plays an essential role in both euchromatic repression and heterochromatic silencing.
| Original language | English |
|---|---|
| Pages (from-to) | 447-458 |
| Number of pages | 12 |
| Journal | Cell |
| Volume | 109 |
| Issue number | 4 |
| DOIs | |
| State | Published - 17 May 2002 |
| Externally published | Yes |
Bibliographical note
Funding Information:We thank Kami Ahmad, Sue Biggins, Toni Bedalov, Dan Gottschling, Mark Groudine, Steve Henikoff, David Ish-Horowicz, Harmit Singh Malik, Suki Parks, Bennett Penn, Steve Tapscott and members of the Parkhurst lab for their advice and interest during the course of this work and for their comments on the manuscript. We also thank A. Bedalov, S. Henikoff, B. Levis, J. Reinitz, B. van Steensel, L. Wallrath, T. Wu, the Berkeley Drosophila Genome Project, Exelixis, and the Bloomington Stock Center for antibodies, DNAs, flies and other reagents used in this study. M.I.R. thanks Taryn Phippen for dangling the dSir2 rotation project carrot and dedicates this paper to the memory of Dr. Rodolfo Rivas. This work was supported by NIH T32 training grant GM07270 (to M.I.R.) and by NIH grant GM47852 (to S.M.P).