Epigenetic regulation of Sox4 during palate development
Identifieur interne : 005808 ( Ncbi/Checkpoint ); précédent : 005807; suivant : 005809Epigenetic regulation of Sox4 during palate development
Auteurs : Ratnam S. Seelan [États-Unis] ; Partha Mukhopadhyay [États-Unis] ; Dennis R. Warner [États-Unis] ; Cynthia L. Webb [États-Unis] ; Michele Pisano [États-Unis] ; Robert M. Greene [États-Unis]Source :
- Epigenomics [ 1750-1911 ] ; 2013.
Abstract
Identification of genes that contribute to secondary palate development provide a better understanding of the etiology of palatal clefts. Gene-expression profiling of the murine palate from gestational days 12–14 (GD12–14), a critical period in palate development, identified
Spatiotemporal analysis revealed that
Our studies indicate that
Url:
DOI: 10.2217/epi.13.1
PubMed: 23566091
PubMed Central: 3776497
Affiliations:
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during palate development</title>
<author><name sortKey="Seelan, Ratnam S" sort="Seelan, Ratnam S" uniqKey="Seelan R" first="Ratnam S" last="Seelan">Ratnam S. Seelan</name>
<affiliation wicri:level="1"><nlm:aff id="A1">University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202</wicri:regionArea>
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<author><name sortKey="Mukhopadhyay, Partha" sort="Mukhopadhyay, Partha" uniqKey="Mukhopadhyay P" first="Partha" last="Mukhopadhyay">Partha Mukhopadhyay</name>
<affiliation wicri:level="1"><nlm:aff id="A1">University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Webb, Cynthia L" sort="Webb, Cynthia L" uniqKey="Webb C" first="Cynthia L" last="Webb">Cynthia L. Webb</name>
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<author><name sortKey="Pisano, Michele" sort="Pisano, Michele" uniqKey="Pisano M" first="Michele" last="Pisano">Michele Pisano</name>
<affiliation wicri:level="1"><nlm:aff id="A1">University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Greene, Robert M" sort="Greene, Robert M" uniqKey="Greene R" first="Robert M" last="Greene">Robert M. Greene</name>
<affiliation wicri:level="1"><nlm:aff id="A1">University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202, USA</nlm:aff>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Epigenetic regulation of <italic>Sox4</italic>
during palate development</title>
<author><name sortKey="Seelan, Ratnam S" sort="Seelan, Ratnam S" uniqKey="Seelan R" first="Ratnam S" last="Seelan">Ratnam S. Seelan</name>
<affiliation wicri:level="1"><nlm:aff id="A1">University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202</wicri:regionArea>
<wicri:noRegion>KY 40202</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mukhopadhyay, Partha" sort="Mukhopadhyay, Partha" uniqKey="Mukhopadhyay P" first="Partha" last="Mukhopadhyay">Partha Mukhopadhyay</name>
<affiliation wicri:level="1"><nlm:aff id="A1">University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202</wicri:regionArea>
<wicri:noRegion>KY 40202</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Warner, Dennis R" sort="Warner, Dennis R" uniqKey="Warner D" first="Dennis R" last="Warner">Dennis R. Warner</name>
<affiliation wicri:level="1"><nlm:aff id="A1">University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202</wicri:regionArea>
<wicri:noRegion>KY 40202</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Webb, Cynthia L" sort="Webb, Cynthia L" uniqKey="Webb C" first="Cynthia L" last="Webb">Cynthia L. Webb</name>
<affiliation wicri:level="1"><nlm:aff id="A1">University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202</wicri:regionArea>
<wicri:noRegion>KY 40202</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pisano, Michele" sort="Pisano, Michele" uniqKey="Pisano M" first="Michele" last="Pisano">Michele Pisano</name>
<affiliation wicri:level="1"><nlm:aff id="A1">University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202</wicri:regionArea>
<wicri:noRegion>KY 40202</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Greene, Robert M" sort="Greene, Robert M" uniqKey="Greene R" first="Robert M" last="Greene">Robert M. Greene</name>
<affiliation wicri:level="1"><nlm:aff id="A1">University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Louisville, Birth Defects Center, Department of Molecular, Cellular & Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202</wicri:regionArea>
<wicri:noRegion>KY 40202</wicri:noRegion>
</affiliation>
</author>
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<series><title level="j">Epigenomics</title>
<idno type="ISSN">1750-1911</idno>
<idno type="eISSN">1750-192X</idno>
<imprint><date when="2013">2013</date>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Aim</title>
<p id="P1">Identification of genes that contribute to secondary palate development provide a better understanding of the etiology of palatal clefts. Gene-expression profiling of the murine palate from gestational days 12–14 (GD12–14), a critical period in palate development, identified <italic>Sox4</italic>
as a differentially expressed gene. In this study, we have examined if the differential expression of <italic>Sox4</italic>
in the palate is due to changes in DNA methylation.</p>
</sec>
<sec id="S2"><title>Materials & methods</title>
<p id="P2"><italic>In situ</italic>
hybridization analysis was used to localize the expression of <italic>Sox4</italic>
in the developing murine secondary palate. CpG methylation profiling of a 1.8-kb upstream region of <italic>Sox4</italic>
in the secondary palate from GD12–14 and transfection analysis in murine embryonic maxillary mesenchymal cells using <italic>Sox4</italic>
deletion, mutant and <italic>in vitro</italic>
methylated plasmid constructs were used to identify critical CpG residues regulating <italic>Sox4</italic>
expression in the palate.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Spatiotemporal analysis revealed that <italic>Sox4</italic>
is expressed in the medial edge epithelium and presumptive rugae-forming regions of the palate from GD12 to GD13. Following palatal shelf fusion on GD14, <italic>Sox4</italic>
was expressed exclusively in the epithelia of the palatal rugae, structures that serve as signaling centers for the anteroposterior extension of the palate, and that are thought to serve as neural stem cell niches. Methylation of a 1.8-kb region upstream of <italic>Sox4</italic>
, containing the putative promoter, completely eliminated promoter activity. CpG methylation profiling of the 1.8-kb region identified a CpG-poor region (DMR4) that exhibited significant differential methylation during palate development, consistent with changes in <italic>Sox4</italic>
mRNA expression. Changes in the methylation of DMR4 were attributed primarily to CpGs 83 and 85.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">Our studies indicate that <italic>Sox4</italic>
is an epigenetically regulated gene that likely integrates multiple signaling systems for mediating palatal fusion, palatal extension and/or the maintenance of the neural stem cell niche in the rugae.</p>
</sec>
</div>
</front>
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<tree><country name="États-Unis"><noRegion><name sortKey="Seelan, Ratnam S" sort="Seelan, Ratnam S" uniqKey="Seelan R" first="Ratnam S" last="Seelan">Ratnam S. Seelan</name>
</noRegion>
<name sortKey="Greene, Robert M" sort="Greene, Robert M" uniqKey="Greene R" first="Robert M" last="Greene">Robert M. Greene</name>
<name sortKey="Mukhopadhyay, Partha" sort="Mukhopadhyay, Partha" uniqKey="Mukhopadhyay P" first="Partha" last="Mukhopadhyay">Partha Mukhopadhyay</name>
<name sortKey="Pisano, Michele" sort="Pisano, Michele" uniqKey="Pisano M" first="Michele" last="Pisano">Michele Pisano</name>
<name sortKey="Warner, Dennis R" sort="Warner, Dennis R" uniqKey="Warner D" first="Dennis R" last="Warner">Dennis R. Warner</name>
<name sortKey="Webb, Cynthia L" sort="Webb, Cynthia L" uniqKey="Webb C" first="Cynthia L" last="Webb">Cynthia L. Webb</name>
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