HMGCR gene expression

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Reaction [omitted]
Homo sapiens
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Cholesterol is highly enriched in the Schwann cell membrane and it plays an essential role in the maturation of MPZ, a key protein component of the compact myelin sheath (Saher and Simons, 2010). The cholesterol of the myelin sheath is synthesized within the Schwann cells, rather than being absorbed from the blood (Jurevics and Morell, 1994; Jurevics et al, 1998). Consistent with this, a number of genes involved in the cholesterol biosynthesis pathway are upregulated during the myelination program, including HMG synthase and HMG coenzyme-A reductase (HMGCR) (Nagarjan et al, 2001; Verheijen et al, 2003; Le Blanc et al, 2005; Jang et al, 2010; Kim et al, 2016; reviewed in Camargo et al, 2009). Myelin-specific expression of HMGCR depends on binding of sterol response binding factor 2 (SREBF2) to its cognate SRE site in the HMGCR promoter (Vallett et al, 1996; Pai et al, 1998; LeBlanc et al, 2005). SREBF2-dependent expression of HMGCR is increased with co-expression of EGR2, suggesting that the transcription factors synergistically activate expression (LeBlanc et al, 2005).

Literature References
PubMed ID Title Journal Year
19143832 SREBPs: SREBP function in glia-neuron interactions

Camargo, N, Verheijen, MH, Smit, AB

FEBS J. 2009
21044070 Locus-wide identification of Egr2/Krox20 regulatory targets in myelin genes

Nagarajan, R, Keles, S, Jones, EA, Sun, G, Chang, LW, Svaren, J, Jang, SW, Srinivasan, R, Krueger, C

J. Neurochem. 2010
15836632 Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination

Wrabetz, L, Gillian-Daniel, AL, Mager, GM, Ferri, C, Svaren, J, Leblanc, SE, Srinivasan, R

J. Neurochem. 2005
14522948 Local regulation of fat metabolism in peripheral nerves

Verheijen, MH, Chrast, R, Burrola, P, Lemke, G

Genes Dev. 2003
9482253 Regenerating sciatic nerve does not utilize circulating cholesterol

Toews, AD, Morell, P, Bouldin, TW, Jurevics, H

Neurochem. Res. 1998
29748249 Maf links Neuregulin1 signaling to cholesterol synthesis in myelinating Schwann cells

Kim, M, Wende, H, Walcher, J, Lewin, GR, Selbach, M, Kempa, S, K├╝hnemund, J, Birchmeier, C, McShane, E, Cheret, C

Genes Dev. 2018
8138712 Sources of cholesterol for kidney and nerve during development

Morell, P, Jurevics, HA

J. Lipid Res. 1994
8647822 A direct role for sterol regulatory element binding protein in activation of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene

Rosenfeld, JM, Osborne, TF, Sanchez, HB, Vallett, SM

J Biol Chem 1996
20213556 Cholesterol and myelin biogenesis

Simons, M, Saher, G

Subcell. Biochem. 2010
9748295 Differential stimulation of cholesterol and unsaturated fatty acid biosynthesis in cells expressing individual nuclear sterol regulatory element-binding proteins

Brown, MS, Pai, JT, Guryev, O, Goldstein, JL

J Biol Chem 1998
11394999 EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression

Milbrandt, J, Watson, M, Le, N, Svaren, J, Nagarajan, R, Araki, T

Neuron 2001
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