title: Interaction between γ-radiation and dietary folate starvation metabolically reprograms global hepatic histone H3 methylation at lysine 4 and lysine 27 residues.
abstract: The objective of the present study was to investigate the regulatory control of histone H3 methylation at lysine 4 (H3K4) and lysine 27 (H3K27) residues in response to the effect of folate deficiency and gamma (γ)-radiation. Male Swiss mice maintained on folate sufficient diet (FSD) and folate free diet (FFD) based on AIN-93M formula, were subjected to 2-4 Gy total body γ-irradiation. There was a significant decrease in liver folate levels with concomitant depletion of S-adenosylmethionine (SAM) reserves. Folate deficiency and γ-radiation together induced H3K4 histone methyltransferase (H3K4HMTase) and suppressed H3K27 histone methyltransferase (H3K27HMTase) activities in a dose and time dependent manner. Our studies suggested radiation induced metabolic reprogramming of H3K4/H3K27 methylation patterns in FFD animals. We showed that radiation toxicity diverted one-carbon (C1) flux in FFD fed animals towards H3K4 methylation. Present work on methylation pattern of histone lysine residues gains particular importance as methylation of H3K4 residues is associated with euchromatin while methylated H3K27 residues promote gene silencing. In conclusion, our study suggests that maintenance of genomic histone methylation under γ-radiation stress might be a very dynamic, progressive process that could be modulated by dietary folate deficiency leading to formation of epigenetically reprogrammed cells.
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India. batravipen@gmail.com
authors.forename: Vipen
authors.initials: V
authors.lastname: Batra
authors.forename: Thomas Paul Asir
authors.initials: TP
authors.lastname: Devasagayam
mesh_terms: D000818:Animals; D004790:Enzyme Induction; D005492:Folic Acid / Q000378:metabolism*; D005720:Gamma Rays; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D008239:Lysine / Q000378:metabolism*; D008297:Male; D008745:Methylation; D051379:Mice
chemical_list: D006657:Histones; D005492:Folic Acid; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine