Epigenetic Blocking of an Enhancer Region Controls Irradiation-Induced Proapoptotic Gene Expression in Drosophila Embryos

• DOI: 10.1016/j.devcel.2008.01.018
• Publication Date: 2008-04-15T13:20:47Z
• Authors: Yanping Zhang; Nianwei Lin; Pamela M. Carroll; Gina Chan; Bo Guan; Hong Xiao; Bing Yao; Samuel S. Wu; Lei Zhou
• Keywords: 570; cellcycle; Embryo, Nonmammalian; Apoptosis; CELLCYCLE; Histone Deacetylases; Epigenesis, Genetic; Histones; 03 medical and health sciences; Animals; Deoxyribonuclease I; Drosophila Proteins; Promoter Regions, Genetic; Oligonucleotide Array Sequence Analysis; Polycomb Repressive Complex 1; 0303 health sciences; Gene Expression Profiling; Neuropeptides; Polycomb Repressive Complex 2; DNA; Histone-Lysine N-Methyltransferase; Chromatin; Repressor Proteins; Drosophila melanogaster; Enhancer Elements, Genetic; Gamma Rays; Developmental Biology

Drosophila embryos are highly sensitive to gamma-ray-induced apoptosis at early but not later, more differentiated stages during development. Two proapoptotic genes, reaper and hid, are upregulated rapidly following irradiation. However, in post-stage-12 embryos, in which most cells have begun differentiation, neither proapoptotic gene can be induced by high doses of irradiation. Our study indicates that the sensitive-to-resistant transition is due to epigenetic blocking of the irradiation-responsive enhancer region (IRER), which is located upstream of reaper but is also required for the induction of hid in response to irradiation. This IRER, but not the transcribed regions of reaper/hid, becomes enriched for trimethylated H3K27/H3K9 and forms a heterochromatin-like structure during the sensitive-to-resistant transition. The functions of histone-modifying enzymes Hdac1(rpd3) and Su(var)3-9 and PcG proteins Su(z)12 and Polycomb are required for this process. Thus, direct epigenetic regulation of two proapoptotic genes controls cellular sensitivity to cytotoxic stimuli.