Epigenetic regulation of oxysterol formation

Meaney, Steve

doi:10.1016/j.biochi.2012.08.020

Cited by 4 publications

(5 citation statements)

References 59 publications

(78 reference statements)

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“…As part of these pathways a class of compounds called oxysterols (or cholesterol oxidation products) are generated, each of which contains one or more additional oxygen containing functional groups. The enzymes responsible for the formation of these oxysterols (i.e., genes responsible for oxysterol synthesis, GROS) are unevenly distributed across different cells and tissues in the body, e.g., CYP7A1 is liver specific while CYP46A1 is found in CNS neurons only (Meaney, 2013). In similarity with the situation for ABCG5/ABCG8 and NPC1L1 above, epigenetic mechanisms have been shown to have a role in the regulation of these genes.…”

Section: Cholesterol Eliminationmentioning

confidence: 99%

“…Given the highly restricted expression of CYP46A1 – in healthy brain it is only present in neurons – this mechanism may represent a supression mechanism important for cell-specificity of CYP46A1 . In addition, the RE1-silencing transcription factor ( REST , also known as NRSF) may play a role in the suppression of CYP46A1 in non-neuronal cells (Meaney, 2013). Although the CYP46A1 promoter is GC rich and contains several predicted CpG islands it does not appear that these are methylated.…”

Section: Cholesterol Eliminationmentioning

confidence: 99%

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Epigenetic regulation of cholesterol homeostasis

Meaney

2014

Front. Genet.

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Although best known as a risk factor for cardiovascular disease, cholesterol is a vital component of all mammalian cells. In addition to key structural roles, cholesterol is a vital biochemical precursor for numerous biologically important compounds including oxysterols and bile acids, as well as acting as an activator of critical morphogenic systems (e.g., the Hedgehog system). A variety of sophisticated regulatory mechanisms interact to coordinate the overall level of cholesterol in cells, tissues and the entire organism. Accumulating evidence indicates that in additional to the more “traditional” regulatory schemes, cholesterol homeostasis is also under the control of epigenetic mechanisms such as histone acetylation and DNA methylation. The available evidence supporting a role for these mechanisms in the control of cholesterol synthesis, elimination, transport and storage are the focus of this review.

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Section: Cholesterol Eliminationmentioning

confidence: 99%

Section: Cholesterol Eliminationmentioning

confidence: 99%

Epigenetic regulation of cholesterol homeostasis

Meaney

2014

Front. Genet.

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“…Based on our and other precious studies, liver modulates cholesterol transport, biosynthesis and transformation in pigs predominantly via epigenetic regulation (20,21). We chose CYP7a1 and HMGCR for epigenetic because the promoter sequences of these two genes can be used in pigs and both of them are key enzymes in the cholesterol metabolism (20,29,30).…”

Section: Discussionmentioning

confidence: 99%

“…Activation of the CYP7a1 gene is associated with an increase in H3 acetylation and H3K4me3 and a decrease in H3K9me1 and H3K27me3. Meanwhile, the activation of HMGCR transcription is accompanied by an increase in H3 acetylation and a decrease in histones H3, H3K9me1, and H3K27me3 (21)(22)(23)(24). Based on these studies, we hypothesized that epigenetic events have a crucial function in modifying liver cholesterol metabolism in Large White and Erhualian piglets.…”

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confidence: 99%

“…Meaney provide a clue that DNA acylation has a key role in the overall coordination of cholesterol homeostasis (19). Different species modifies hepatic cholesterol metabolic gene transcription by DNA methylation and histones modification like H3K4me3, H3K27me3, and H3K9me1 (19)(20)(21). Activation of the CYP7a1 gene is associated with an increase in H3 acetylation and H3K4me3 and a decrease in H3K9me1 and H3K27me3.…”

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Epigenetic Regulation of Key Enzymes CYP7a1 and HMGCR Affect Hepatic Cholesterol Metabolism in Different Breeds of Piglets

Xiao

Jian

et al. 2020

Front. Vet. Sci.

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Liver is the place where cholesterol is synthesized, transported, secreted, and transformed, thus liver takes an irreplaceable role in cholesterol homeostasis. Hepatic cholesterol metabolism differs between breeds, yet the molecular mechanism is unclear. In this study Large White (LW) and Erhualian (EHL) piglets (at birth and 25-day-old) were used, 6 each time point per breed. Erhualian piglets had significantly lower body and liver weight compared with Large White at birth and weaning, but the liver/ body weight ratio was higher at weaning, associated with increased serum and liver cholesterol and triglyceride content. The mRNA expression of Cholesterol-7alpha-hydroxylase (CYP7a1) and Recombinant Acetyl Coenzyme Acetyltransferase 2 (ACAT2) were down-regulated in Erhualian piglets at birth, while hepatic Sterol-regulatory element binding protein 2 (SREBP2) mRNA expression was up-regulated in Erhualian piglets at weaning, as well as SREBP2 protein content, compared with Large White piglets. At birth, the depressed CYP7a1 transcription in Erhualian piglets was associated with decreased Histone H3 (H3) and increased Histone H3 lysine 27 trimethylation (H3K27me3). While the results revealed significant promoter hypermethylation of 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) promoter in Erhualian piglets at weaning, together with increased Histone H3 lysine 9 monomethylation (H3K9me1) and Histone H3 lysine 4 trimethylation (H3K4me3). These results suggest that epigenetic modification may be an important mechanism in hepatic cholesterol metabolism among different species, which is vital for maintaining cholesterol homeostasis and decreasing risk of cardiovascular disease.

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