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. 2024 Dec;42(8):e70036.
doi: 10.1002/cbf.70036.

Epigenetic Regulation by Histone Methylation and Demethylation in Freeze-Tolerant Frog Kidney

Olawale O Taiwo  1 , Sarah A Breedon  1 , Kenneth B Storey  1
Affiliations

Epigenetic Regulation by Histone Methylation and Demethylation in Freeze-Tolerant Frog Kidney

Olawale O Taiwo et al. Cell Biochem Funct. 2024 Dec.

Abstract

The wood frog (Rana sylvatica) endures whole-body freezing over the winter, with extensive extracellular ice formation and halted physiological activities. Epigenetic mechanisms, including reversible histone lysine methylation, enable quick alterations in gene expression, helping to maintain viability during freeze-thaw cycles. The present study evaluated eight histone lysine methyltransferases (KMTs), 10 histone lysine demethylases (KDMs), and 11 histone marks in wood frog kidneys. Using immunoblotting, significant changes in relative protein levels of multiple KMTs and KDMs were observed in response to freezing, with variable alterations during thawing. Specifically, the repressive methyl marks H3K27me1 and H4K20me3 significantly decreased during freezing, whereas H3K9me3, H3K27me3, and H3K36me2 decreased during thawing. These results demonstrate that the regulation of histone methylation and demethylation play crucial roles in controlling gene expression over the freeze-thaw cycle and the maintenance of normal renal physiology.

Keywords: Rana sylvatica; freeze tolerance; gene expression; hypometabolism; kidney.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Histone lysine methylation and demethylation, involving the addition or removal of methyl groups (Me) on specific lysine residues of histones H3 and H4, which affects gene expression. Important enzymes involved in methylation are histone methyltransferases (HMTs or KMTs), such as KMT2, SET1A, and SUV39H1, using S‐adenosylmethionine (SAM) as the methyl donor. Demethylation is performed by histone demethylases (KDMs), in the presence of oxygen (O2) and alpha‐ketoglutarate (α‐KG). Methylation states (mono‐, di‐, tri‐methylation) and specific lysine targets (e.g., K4, K9, K27) determine whether gene expression is activated or repressed indicating dynamic regulation of gene activity. Created with BioRender.com.
Figure 2
Figure 2
Relative protein levels of lysine methyltransferases (KMTs) in Rana sylvatica kidney via western immunoblotting. (A) Histogram showing mean ± SEM (n = 4) standardized expression levels under control, 24 h freezing, and 8 h thawed conditions. For each protein target, values that share the same letter designations are not significantly different from one another, while values with different letter designations are significantly different (p < 0.05). (B) Representative western blots for individual targets under each experimental condition. Data were analyzed using a one‐way ANOVA with a Tukey's post hoc test.
Figure 3
Figure 3
Relative protein levels of methylated histone residues in Rana sylvatica kidneys. All other information as in Figure 2.
Figure 4
Figure 4
Relative protein levels of lysine demethylases (KDMs) in Rana sylvatica kidneys. All other information as in Figure 2.
See this image and copyright information in PMC

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