Placenta-specific Methylation of the Vitamin D 24-Hydroxylase Gene
Identifieur interne : 007B74 ( Main/Exploration ); précédent : 007B73; suivant : 007B75Placenta-specific Methylation of the Vitamin D 24-Hydroxylase Gene
Auteurs : Boris Novakovic ; Mandy Sibson ; Hong Kiat Ng [Australie] ; Ursula Manuelpillai ; Vardhman Rakyan ; Thomas Down [Royaume-Uni] ; Stephan Beck [Royaume-Uni] ; Thierry Fournier ; Danielle Evain-Brion ; Eva Dimitriadis [Australie] ; Jeffrey M. Craig [Australie] ; Ruth Morley [Australie] ; Richard Saffery [Australie]Source :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2009.
Abstract
Plasma concentrations of biologically active vitamin D
(1,25-(OH)2D) are tightly controlled via feedback regulation of
renal 1α-hydroxylase (
Url:
DOI: 10.1074/jbc.M809542200
PubMed: 19237542
PubMed Central: 2685665
Affiliations:
- Australie, Royaume-Uni
- Angleterre, Angleterre de l'Est, Grand Londres, Victoria (État)
- Cambridge, Londres, Melbourne
- University College de Londres, Université de Cambridge, Université de Melbourne
Links toward previous steps (curation, corpus...)
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- to stream Pmc, to step Checkpoint: 002742
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- to stream Ncbi, to step Curation: 000540
- to stream Ncbi, to step Checkpoint: 000540
- to stream Main, to step Merge: 008231
- to stream Main, to step Curation: 007B74
Le document en format XML
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<series><title level="j">The Journal of Biological Chemistry</title>
<idno type="ISSN">0021-9258</idno>
<idno type="eISSN">1083-351X</idno>
<imprint><date when="2009">2009</date>
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<front><div type="abstract" xml:lang="en"><p>Plasma concentrations of biologically active vitamin D
(1,25-(OH)<sub>2</sub>
D) are tightly controlled via feedback regulation of
renal 1α-hydroxylase (<italic>CYP27B1</italic>
; positive) and 24-hydroxylase
(<italic>CYP24A1</italic>
; catabolic) enzymes. In pregnancy, this regulation is
uncoupled, and 1,25-(OH)<sub>2</sub>
D levels are significantly elevated,
suggesting a role in pregnancy progression. Epigenetic regulation of
<italic>CYP27B1</italic>
and <italic>CYP24A1</italic>
has previously been described in cell
and animal models, and despite emerging evidence for a critical role of
epigenetics in placentation generally, little is known about the regulation of
enzymes modulating vitamin D homeostasis at the fetomaternal interface. In
this study, we investigated the methylation status of genes regulating vitamin
D bioavailability and activity in the placenta. No methylation of the
<italic>VDR</italic>
(vitamin D receptor) and <italic>CYP27B1</italic>
genes was found in any
placental tissues. In contrast, the <italic>CYP24A1</italic>
gene is methylated in
human placenta, purified cytotrophoblasts, and primary and cultured chorionic
villus sampling tissue. No methylation was detected in any somatic human
tissue tested. Methylation was also evident in marmoset and mouse placental
tissue. All three genes were hypermethylated in choriocarcinoma cell lines,
highlighting the role of vitamin D deregulation in this cancer. Gene
expression analysis confirmed a reduced capacity for <italic>CYP24A1</italic>
induction with promoter methylation in primary cells and <italic>in vitro</italic>
reporter analysis demonstrated that promoter methylation directly
down-regulates basal promoter activity and abolishes vitamin D-mediated
feedback activation. This study strongly suggests that epigenetic decoupling
of vitamin D feedback catabolism plays an important role in maximizing active
vitamin D bioavailability at the fetomaternal interface.</p>
</div>
</front>
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<biblStruct></biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Royaume-Uni</li>
</country>
<region><li>Angleterre</li>
<li>Angleterre de l'Est</li>
<li>Grand Londres</li>
<li>Victoria (État)</li>
</region>
<settlement><li>Cambridge</li>
<li>Londres</li>
<li>Melbourne</li>
</settlement>
<orgName><li>University College de Londres</li>
<li>Université de Cambridge</li>
<li>Université de Melbourne</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Evain Brion, Danielle" sort="Evain Brion, Danielle" uniqKey="Evain Brion D" first="Danielle" last="Evain-Brion">Danielle Evain-Brion</name>
<name sortKey="Fournier, Thierry" sort="Fournier, Thierry" uniqKey="Fournier T" first="Thierry" last="Fournier">Thierry Fournier</name>
<name sortKey="Manuelpillai, Ursula" sort="Manuelpillai, Ursula" uniqKey="Manuelpillai U" first="Ursula" last="Manuelpillai">Ursula Manuelpillai</name>
<name sortKey="Novakovic, Boris" sort="Novakovic, Boris" uniqKey="Novakovic B" first="Boris" last="Novakovic">Boris Novakovic</name>
<name sortKey="Rakyan, Vardhman" sort="Rakyan, Vardhman" uniqKey="Rakyan V" first="Vardhman" last="Rakyan">Vardhman Rakyan</name>
<name sortKey="Sibson, Mandy" sort="Sibson, Mandy" uniqKey="Sibson M" first="Mandy" last="Sibson">Mandy Sibson</name>
</noCountry>
<country name="Australie"><region name="Victoria (État)"><name sortKey="Ng, Hong Kiat" sort="Ng, Hong Kiat" uniqKey="Ng H" first="Hong Kiat" last="Ng">Hong Kiat Ng</name>
</region>
<name sortKey="Craig, Jeffrey M" sort="Craig, Jeffrey M" uniqKey="Craig J" first="Jeffrey M." last="Craig">Jeffrey M. Craig</name>
<name sortKey="Dimitriadis, Eva" sort="Dimitriadis, Eva" uniqKey="Dimitriadis E" first="Eva" last="Dimitriadis">Eva Dimitriadis</name>
<name sortKey="Morley, Ruth" sort="Morley, Ruth" uniqKey="Morley R" first="Ruth" last="Morley">Ruth Morley</name>
<name sortKey="Saffery, Richard" sort="Saffery, Richard" uniqKey="Saffery R" first="Richard" last="Saffery">Richard Saffery</name>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Down, Thomas" sort="Down, Thomas" uniqKey="Down T" first="Thomas" last="Down">Thomas Down</name>
</region>
<name sortKey="Beck, Stephan" sort="Beck, Stephan" uniqKey="Beck S" first="Stephan" last="Beck">Stephan Beck</name>
</country>
</tree>
</affiliations>
</record>
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