Epigenetic regulation of cholesterol homeostasis.

Steve Meaney

doi:10.3389/fgene.2014.00311

Abstract

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.

Highlights

Cholesterol is an ubiquitous 27-carbon steroid and a vital component of cellular membranes in vertebrates (Vance and Vance, 2002)
This review presents a review of the current evidence of the role of epigenetic mechanisms in each of these processes
Studies on epigenetic regulation of CYP27A1 are limited and are descriptive only – 5AZA was shown to have no effect in macrophages (Escher et al, 2005) while trichostatin A (TSA) treatment of HepG2 cells resulted in a six-fold decrease of CYP27A1 mRNA at 24 h followed by a return to basal levels by 48 h (Chittur et al, 2008)

Summary

Introduction

Cholesterol (cholest-5-ene-3β-ol) is an ubiquitous 27-carbon steroid and a vital component of cellular membranes in vertebrates (Vance and Vance, 2002). The data available in connection with these studies indicates that epigenetic mechanisms are important for the regulation of the cholesterol synthesis pathway.

Results

Conclusion