Cross talk between histone 3 acetylation, methylation and phosphorylation by intermittent hypoxia

Autor: Jayasri Nanduri, Ning Wang, Nanduri Prabhakar
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
Popis: We have previously identified histone 3 (H3) post translational modifications, specifically acetylation and methylation as an early epigenetic mechanism associated with sympathetic nerve activation and hypertension in rodent models of intermittent hypoxia (IH), a hallmark feature of sleep apnea (Nanduri et al, Physiol genomics 2021, Ning et al, Front Physiol 2021). Phosphorylation of H3 serine (S) residues that are adjacent to acetylation and methylation sites are also shown to regulate chromatin structure and gene expression. The aim of the present study is to assess whether IH affect H3 phosphorylation and whether phosphorylation influences H3 acetylation by IH. Studies were performed on rat pheochromocytoma (PC12) cells and adrenal chromaffin cells of rats treated with 10d IH as well as heme oxygenase (HO)-2 null mice, which exhibit spontaneous apneas. IH increased H3 lysine (K) 27 acetylation in PC12 cells, rat adrenal chromaffin cells and HO-2 null mice. These effects were associated with dephsophorylation of H3 at S28 and demethylation of K27. Inhibition of S28 dephosphorylation by protein phosphatase inhibitor (PIC) or Calyculin A, a specific inhibitor of protein phosphatase (PP)-1 and -2, inhibited H3K27 acetylation by IH. Conversely, inhibition of K27 acetylation with CTK7A a specific inhibitor of acetyl transferase p300/CBP increased S28 phosphorylation and K27 methylation in IH exposed cells. These results demonstrate that effects of IH on H3 lysine acetylation, methylation and phosphorylation are complex and a cross-talk between the three events regulate IH-induced transcriptional activity. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Databáze: OpenAIRE
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