Sterol dependent regulation of human TM7SF2 gene expression: Role of the encoded 3β-hydroxysterol Δ14-reductase in human cholesterol biosynthesis

Bennati, Anna Maria; Castelli, Marilena; Fazia, Maria Agnese Della; Beccari, Tommaso; Caruso, Donatella; Servillo, Giuseppe; Roberti, Rita

doi:10.1016/j.bbalip.2006.05.004

Cited by 50 publications

(63 citation statements)

References 40 publications

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“…[16,35] It is notable that bone marrow is the body tissue with the highest expression of LBR mRNA. [36] An unexpected observation was the apparent increase on immunoblots of lamin A/C, increasing systematically from +/+ to +/ic (~2.5 fold) to ic/ ic (~6.2 fold). Furthermore, for all three genotypes, ATRA-induced granulocytic differentiation resulted in a decline in the level of lamin A/C.…”

Section: Discussionmentioning

confidence: 97%

Granulocytic nuclear differentiation of lamin B receptor–deficient mouse EPRO cells

Zwerger

Herrmann

Gaines

et al. 2008

Experimental Hematology

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Objective-Lamin B receptor (LBR) is an integral protein of the inner nuclear membrane. Recent studies have demonstrated that genetic deficiency of LBR during granulopoiesis results in hypolobulation of the mature neutrophil nucleus, as observed in human Pelger-Huët anomaly (PHA) and mouse ichthyosis (ic). In this study we have utilized differentiated promyelocytes (EPRO cells) that were derived from the bone marrow of homozygous and heterozygous ichthyosis mice to examine changes to the expression of nuclear envelope proteins and heterochromatin structure that result from deficient LBR expression.Materials and Methods-Wildtype (+/+), heterozygous (+/ic) and homozygous (ic/ic) granulocytic forms of EPRO cells were analyzed for the expression of multiple lamins and inner nuclear envelope proteins by immunostaining and immunoblotting techniques. The heterochromatin architecture was also examined by immunostaining for histone lysine methylation.Results-Wildtype (+/+) and heterozygous (+/ic) granulocytic forms revealed ring-shaped nuclei and contained LBR within the nuclear envelope; ic/ic granulocytes exhibited smaller ovoid nuclei devoid of LBR. The pericentric heterochromatin of undifferentiated and granulocytic ic/ic cells was condensed into larger spots and shifted away from the nuclear envelope, compared to +/+ and +/ic cell forms. Lamin A/C, which is normally not present in mature granulocytes, was significantly elevated in LBR-deficient EPRO cells.Conclusions-Our observations suggest roles for LBR during granulopoiesis which may involve augmenting nuclear membrane growth, facilitating compartmentalization of heterochromatin and promoting down-regulation of lamin A/C expression. Category Granulopoiesis

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Section: Discussionmentioning

confidence: 97%

Granulocytic nuclear differentiation of lamin B receptor–deficient mouse EPRO cells

Zwerger

Herrmann

Gaines

et al. 2008

Experimental Hematology

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“…Moderate levels of expression of lamins A and B2 exhibited nuclear lobulation, with essentially no intranuclear membrane arrays; lamin C, without the CaaX motif did not induce lobulation is worth pointing out that the adult human tissue with the highest level of LBR mRNA expression is bone marrow. 134 There are tantalizing indications of a "connection" between lamin A/C and LBR. Lamin A has been identified in a detergent solubilized "LBR complex" isolated by immunoprecipitation.…”

Section: Conundrums and Speculationsmentioning

confidence: 99%

Lamin B receptor

Olins

Rhodes²,

Welch³

et al. 2010

Nucleus

134

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“…However, LBR appears to adequately compensate, as cholesterol levels are normal in Tm7sf2 knock-out mice (24). Because TM7SF2 is an SREBP-2 target gene, whereas LBR is not (23), it may be that LBR is constitutive, whereas TM7SF2 encodes the inducible sterol ⌬ 14 -reductase activity. Three isoforms of SREBP exist, with the SREBP-2 isoform being ascribed the major role in regulating cholesterol synthetic genes.…”

Section: Transcriptional Regulationmentioning

confidence: 99%

“…Thus, nearly all of the genes encoding cholesterol synthesis enzymes are SREBP targets (Table 1). A notable exception is the lamin B receptor (LBR), a protein of the inner nuclear membrane involved mainly in heterochromatin organization but also possessing sterol ⌬ 14 -reductase activity (23). The principal sterol ⌬ 14 -reductase, located in the endoplasmic reticulum (ER), is DHCR14, encoded by the TM7SF2 (transmembrane 7 superfamily member 2) gene.…”

Section: Transcriptional Regulationmentioning

confidence: 99%

Controlling Cholesterol Synthesis beyond 3-Hydroxy-3-methylglutaryl-CoA Reductase (HMGCR)

Sharpe

Brown

2013

Journal of Biological Chemistry

298

251

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Sterol dependent regulation of human TM7SF2 gene expression: Role of the encoded 3β-hydroxysterol Δ14-reductase in human cholesterol biosynthesis

Cited by 50 publications

References 40 publications

Granulocytic nuclear differentiation of lamin B receptor–deficient mouse EPRO cells

Granulocytic nuclear differentiation of lamin B receptor–deficient mouse EPRO cells

Lamin B receptor

Controlling Cholesterol Synthesis beyond 3-Hydroxy-3-methylglutaryl-CoA Reductase (HMGCR)

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