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Co-Localization of DNA i-Motif-Forming Sequences and 5-Hydroxymethyl-cytosines in Human Embryonic Stem Cells
G-quadruplexes (G4s) and i-motifs (iMs) are tetraplex DNA structures. Sequences capable of forming G4/iMs are abundant near the transcription start sites (TSS) of several genes. G4/iMs affect gene expression in vitro. Depending on the gene, the presence of G4/iMs can enhance or suppress expression,...
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Published in: | Molecules (Basel, Switzerland) Switzerland), 2019-10, Vol.24 (19), p.3619 |
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description | G-quadruplexes (G4s) and i-motifs (iMs) are tetraplex DNA structures. Sequences capable of forming G4/iMs are abundant near the transcription start sites (TSS) of several genes. G4/iMs affect gene expression in vitro. Depending on the gene, the presence of G4/iMs can enhance or suppress expression, making it challenging to discern the underlying mechanism by which they operate. Factors affecting G4/iM structures can provide additional insight into their mechanism of regulation. One such factor is epigenetic modification. The 5-hydroxymethylated cytosines (5hmCs) are epigenetic modifications that occur abundantly in human embryonic stem cells (hESC). The 5hmCs, like G4/iMs, are known to participate in gene regulation and are also enriched near the TSS. We investigated genomic co-localization to assess the possibility that these two elements may play an interdependent role in regulating genes in hESC. Our results indicate that amongst 15,760 G4/iM-forming locations, only 15% have 5hmCs associated with them. A detailed analysis of G4/iM-forming locations enriched in 5hmC indicates that most of these locations are in genes that are associated with cell differentiation, proliferation, apoptosis and embryogenesis. The library generated from our analysis is an important resource for investigators exploring the interdependence of these DNA features in regulating expression of selected genes in hESC. |
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Sequences capable of forming G4/iMs are abundant near the transcription start sites (TSS) of several genes. G4/iMs affect gene expression in vitro. Depending on the gene, the presence of G4/iMs can enhance or suppress expression, making it challenging to discern the underlying mechanism by which they operate. Factors affecting G4/iM structures can provide additional insight into their mechanism of regulation. One such factor is epigenetic modification. The 5-hydroxymethylated cytosines (5hmCs) are epigenetic modifications that occur abundantly in human embryonic stem cells (hESC). The 5hmCs, like G4/iMs, are known to participate in gene regulation and are also enriched near the TSS. We investigated genomic co-localization to assess the possibility that these two elements may play an interdependent role in regulating genes in hESC. Our results indicate that amongst 15,760 G4/iM-forming locations, only 15% have 5hmCs associated with them. A detailed analysis of G4/iM-forming locations enriched in 5hmC indicates that most of these locations are in genes that are associated with cell differentiation, proliferation, apoptosis and embryogenesis. The library generated from our analysis is an important resource for investigators exploring the interdependence of these DNA features in regulating expression of selected genes in hESC.</description><identifier>ISSN: 1420-3049</identifier><identifier>EISSN: 1420-3049</identifier><identifier>DOI: 10.3390/molecules24193619</identifier><identifier>PMID: 31597270</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>5-Methylcytosine - analogs & derivatives ; 5-Methylcytosine - chemistry ; Apoptosis ; Base Composition ; Cell differentiation ; Cell Differentiation - genetics ; Cell Proliferation - genetics ; CpG Islands ; cytosine-rich dna ; Deoxyribonucleic acid ; Differentiation (biology) ; DNA ; DNA Methylation ; dna nanomaterials ; dna secondary structures ; Embryo cells ; Embryogenesis ; Embryonic growth stage ; Epigenesis, Genetic ; Epigenetics ; G-Quadruplexes ; Gene expression ; Gene regulation ; Genes ; Genomes ; Human Embryonic Stem Cells - cytology ; Human Embryonic Stem Cells - metabolism ; Humans ; Localization ; Nanostructures - chemistry ; Nucleic Acid Conformation ; Nucleotide Motifs ; Nucleotide sequence ; Physiology ; Stem cells ; Transcription ; Transcription Initiation Site</subject><ispartof>Molecules (Basel, Switzerland), 2019-10, Vol.24 (19), p.3619</ispartof><rights>2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-673c68c3502cad59a677d2b96f3f24b275dade30977bad3f3bbee32d830f05093</citedby><cites>FETCH-LOGICAL-c493t-673c68c3502cad59a677d2b96f3f24b275dade30977bad3f3bbee32d830f05093</cites><orcidid>0000-0002-3933-2200</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2549051008/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2549051008?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31597270$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bhavsar-Jog, Yogini P</creatorcontrib><creatorcontrib>Van Dornshuld, Eric</creatorcontrib><creatorcontrib>Brooks, Tracy A</creatorcontrib><creatorcontrib>Tschumper, Gregory S</creatorcontrib><creatorcontrib>Wadkins, Randy M</creatorcontrib><title>Co-Localization of DNA i-Motif-Forming Sequences and 5-Hydroxymethyl-cytosines in Human Embryonic Stem Cells</title><title>Molecules (Basel, Switzerland)</title><addtitle>Molecules</addtitle><description>G-quadruplexes (G4s) and i-motifs (iMs) are tetraplex DNA structures. Sequences capable of forming G4/iMs are abundant near the transcription start sites (TSS) of several genes. G4/iMs affect gene expression in vitro. Depending on the gene, the presence of G4/iMs can enhance or suppress expression, making it challenging to discern the underlying mechanism by which they operate. Factors affecting G4/iM structures can provide additional insight into their mechanism of regulation. One such factor is epigenetic modification. The 5-hydroxymethylated cytosines (5hmCs) are epigenetic modifications that occur abundantly in human embryonic stem cells (hESC). The 5hmCs, like G4/iMs, are known to participate in gene regulation and are also enriched near the TSS. We investigated genomic co-localization to assess the possibility that these two elements may play an interdependent role in regulating genes in hESC. Our results indicate that amongst 15,760 G4/iM-forming locations, only 15% have 5hmCs associated with them. A detailed analysis of G4/iM-forming locations enriched in 5hmC indicates that most of these locations are in genes that are associated with cell differentiation, proliferation, apoptosis and embryogenesis. The library generated from our analysis is an important resource for investigators exploring the interdependence of these DNA features in regulating expression of selected genes in hESC.</description><subject>5-Methylcytosine - analogs & derivatives</subject><subject>5-Methylcytosine - chemistry</subject><subject>Apoptosis</subject><subject>Base Composition</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>CpG Islands</subject><subject>cytosine-rich dna</subject><subject>Deoxyribonucleic acid</subject><subject>Differentiation (biology)</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>dna nanomaterials</subject><subject>dna secondary structures</subject><subject>Embryo cells</subject><subject>Embryogenesis</subject><subject>Embryonic growth stage</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>G-Quadruplexes</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genomes</subject><subject>Human Embryonic Stem Cells - cytology</subject><subject>Human Embryonic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Localization</subject><subject>Nanostructures - chemistry</subject><subject>Nucleic Acid Conformation</subject><subject>Nucleotide Motifs</subject><subject>Nucleotide sequence</subject><subject>Physiology</subject><subject>Stem cells</subject><subject>Transcription</subject><subject>Transcription Initiation Site</subject><issn>1420-3049</issn><issn>1420-3049</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNplkk9v1DAQxSMEoqXwAbggS1y4hI7_xfEFqVpattJSDoWz5djO1ivHLnZSET49gW2rlp7Gmnnz0_jpVdVbDB8plXA8pODMFFwhDEvaYPmsOsSMQE2ByecP3gfVq1J2AAQzzF9WBxRzKYiAwyqsUr1JRgf_W48-RZR69PniBPn6axp9X5-lPPi4RZfu5-SicQXpaBGv17PN6dc8uPFqDrWZx1R8XKY-ovU06IhOhy7PKXqDLkc3oJULobyuXvQ6FPfmth5VP85Ov6_W9ebbl_PVyaY2TNKxbgQ1TWsoB2K05VI3QljSyaanPWEdEdxq6yhIITptaU-7zjlKbEuhBw6SHlXne65Neqeusx90nlXSXv1rpLxVOo_eBKeE6ZxsWk6gIazHWhKppXSEt6Y1TUcW1qc963rqBmeNi2PW4RH08ST6K7VNN6ppgQEXC-DDLSCnxcMyqsEXs9iho0tTUYQCFUy2hC3S9_9Jd2nKcbFKEc4kcAzQLiq8V5mcSsmuvz8Gg_qbC_UkF8vOu4e_uN-4CwL9A6BWtkI</recordid><startdate>20191008</startdate><enddate>20191008</enddate><creator>Bhavsar-Jog, Yogini P</creator><creator>Van Dornshuld, Eric</creator><creator>Brooks, Tracy A</creator><creator>Tschumper, Gregory S</creator><creator>Wadkins, Randy M</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3933-2200</orcidid></search><sort><creationdate>20191008</creationdate><title>Co-Localization of DNA i-Motif-Forming Sequences and 5-Hydroxymethyl-cytosines in Human Embryonic Stem Cells</title><author>Bhavsar-Jog, Yogini P ; 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Sequences capable of forming G4/iMs are abundant near the transcription start sites (TSS) of several genes. G4/iMs affect gene expression in vitro. Depending on the gene, the presence of G4/iMs can enhance or suppress expression, making it challenging to discern the underlying mechanism by which they operate. Factors affecting G4/iM structures can provide additional insight into their mechanism of regulation. One such factor is epigenetic modification. The 5-hydroxymethylated cytosines (5hmCs) are epigenetic modifications that occur abundantly in human embryonic stem cells (hESC). The 5hmCs, like G4/iMs, are known to participate in gene regulation and are also enriched near the TSS. We investigated genomic co-localization to assess the possibility that these two elements may play an interdependent role in regulating genes in hESC. Our results indicate that amongst 15,760 G4/iM-forming locations, only 15% have 5hmCs associated with them. A detailed analysis of G4/iM-forming locations enriched in 5hmC indicates that most of these locations are in genes that are associated with cell differentiation, proliferation, apoptosis and embryogenesis. The library generated from our analysis is an important resource for investigators exploring the interdependence of these DNA features in regulating expression of selected genes in hESC.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31597270</pmid><doi>10.3390/molecules24193619</doi><orcidid>https://orcid.org/0000-0002-3933-2200</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 5-Methylcytosine - analogs & derivatives 5-Methylcytosine - chemistry Apoptosis Base Composition Cell differentiation Cell Differentiation - genetics Cell Proliferation - genetics CpG Islands cytosine-rich dna Deoxyribonucleic acid Differentiation (biology) DNA DNA Methylation dna nanomaterials dna secondary structures Embryo cells Embryogenesis Embryonic growth stage Epigenesis, Genetic Epigenetics G-Quadruplexes Gene expression Gene regulation Genes Genomes Human Embryonic Stem Cells - cytology Human Embryonic Stem Cells - metabolism Humans Localization Nanostructures - chemistry Nucleic Acid Conformation Nucleotide Motifs Nucleotide sequence Physiology Stem cells Transcription Transcription Initiation Site |
title | Co-Localization of DNA i-Motif-Forming Sequences and 5-Hydroxymethyl-cytosines in Human Embryonic Stem Cells |
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