Epigenetic blocking of an enhancer region controls irradiation-induced proapoptotic gene expression in Drosophila embryos.
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.
Zhang
Yanping
Y
Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Lin
Nianwei
N
Carroll
Pamela M
PM
Chan
Gina
G
Guan
Bo
B
Xiao
Hong
H
Yao
Bing
B
Wu
Samuel S
SS
Zhou
Lei
L
D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D002843:Chromatin / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology / Q000528:radiation effects; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D005720:Gamma Rays; D020869:Gene Expression Profiling; D006655:Histone Deacetylases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins
D002843:Chromatin; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D006657:Histones; D009479:Neuropeptides; C066770:Pc protein, Drosophila; D012097:Repressor Proteins; C543390:Su(z)12 protein, Drosophila; C086973:rpr protein, Drosophila; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1; D003850:Deoxyribonuclease I; D006655:Histone Deacetylases