drosophila histone deacetylase-3 controls imaginal disc size through suppression of apoptosis果蝇成虫盘组蛋白deacetylase-3控件大小通过抑制细胞凋亡.pdfVIP

Drosophila Histone Deacetylase-3 Controls Imaginal Disc Size through Suppression of Apoptosis 1,2. 1,2. 1,2 1 Changqi C. Zhu , Douglas J. Bornemann , David Zhitomirsky , Ellen L. Miller , Michael B. 1,2 1 O’Connor , Jeffrey A. Simon * 1 Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, United States of America, 2 Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America Abstract Histone deacetylases (HDACs) execute biological regulation through post-translational modification of chromatin and other cellular substrates. In humans, there are eleven HDACs, organized into three distinct subfamilies. This large number of HDACs raises questions about functional overlap and division of labor among paralogs. In vivo roles are simpler to address in Drosophila, where there are only five HDAC family members and only two are implicated in transcriptional control. Of these two, HDAC1 has been characterized genetically, but its most closely related paralog, HDAC3, has not. Here we describe the isolation and phenotypic characterization of hdac3 mutations. We find that both hdac3 and hdac1 mutations are dominant suppressors of position effect variegation, suggesting functional overlap in heterochromatin regulation. However, all five hdac3 loss-of-function alleles are recessive lethal during larval/pupal stages, indicating that HDAC3 is essential on its own for Drosophila development. The mutant larvae display small imaginal discs, which result from abnormally elevated levels of apoptosis. This cell death occurs as a cell