Melatonin ameliorates histone modification disorders in mammalian aged oocytes by neutralizing the alkylation of HDAC1

Free Radic Biol Med. 2023 Aug 23:S0891-5849(23)00603-2. doi: 10.1016/j.freeradbiomed.2023.08.023. Online ahead of print.ABSTRACTAging-associated histone modification changes in oocytes have been sporadically reported, but the underlying mechanisms remain elusive. Here, we systematically characterize multiple histone modifications in oocytes during aging. We find that maternal and postovulatory aging markedly alter the status of histone modifications, specifically H4K12ac and H3K4me3, in both mouse and porcine oocytes. Meanwhile, we identify a substantial reduction in HDAC1 (histone deacetylase 1) protein in aged oocytes, which contributes to the changes in H4K12ac and H3K4me3. Moreover, by employing methylglyoxal (MG) and site-directed mutagenesis, we demonstrate that the elevated reactive carbonyl species (RCS) level induces HDAC1 degradation, likely through attacking the cysteine residues, thereby influences histone modification state. Importantly, supplementation of melatonin not only prevents the loss of HDAC1 protein, but also partially corrects the H4K12ac and H3K4me3 status in aged oocytes. To sum up, this study established the link between redox disequilibrium and histone modification alterations during mammalian oocyte aging.PMID:37625658 | DOI:10.1016/j.freeradbiomed.2023.08.023

Source: Free Radical Biology and Medicine - August 25, 2023 Category: Biology Authors: Yongfu He Ming Gao Weizheng Yang Shaochen Sun Qiang Wang Ling Gu Source Type: research