Epigenetics in anoxia tolerance: a role for histone deacetylases.
The importance of epigenetics has been established in many key biological processes but the relevance of this regulatory mechanism to animal survival of low oxygen conditions has never been examined. To establish whether epigenetic mechanisms could be involved in natural anoxia tolerance, we have examined the anoxia-responsive expression of the transcriptional silencers, histone deacetylases (HDACs), in tissues of a unique model for anoxia tolerance, the freshwater turtle Trachemys scripta elegans. Transcript and protein levels of all five HDACs rose by 1.3-4.6 and 1.7-3.5-fold, respectively, in skeletal muscle in response to 20 h of anoxia exposure. In addition, HDAC activity in the muscle increased by 1.5-fold in response to 20 h of anoxia and levels of acetylated histone H3 (Lys 9 or Lys 23) decreased to 40-60% of control values. The liver displayed a milder response with HDAC1, -4, and -5 protein levels increasing by 1.6-2.1-fold after 5 h anoxia exposure; acetylated histone H3 levels also decreased to 50-75% of control values. Only HDAC5 responded to anoxia exposure in the heart; Hdac5 transcript levels increased 2.1-2.3-fold and HDAC5 protein rose by 3.3-fold. Overall, our results show a tissue-specific pattern of HDAC upregulation in response to anoxia exposure in T.s. elegans, suggesting that these enzymes play a key role in anoxia tolerance, probably by contributing to the transcriptional silencing necessary in this hypometabolic state.
Krivoruchko
Anastasia
A
Institute of Biochemistry, Carleton University, Ottawa, ON, Canada. krivoruchko@gmail.com
Storey
Kenneth B
KB
D000107:Acetylation; D000818:Animals; D015153:Blotting, Western; D044127:Epigenesis, Genetic; D006321:Heart / Q000502:physiology; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D000860:Hypoxia / Q000201:enzymology* / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014426:Turtles
D006657:Histones; D012333:RNA, Messenger; D006655:Histone Deacetylases