HEB and E2A function as SMAD/FOXH1 cofactors
Nodal signaling, mediated through SMAD transcription factors, is necessary for pluripotency maintenance and endoderm commitment. We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. We demons...
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| Veröffentlicht in: | Genes & development 2011-08, Vol.25 (15), p.1654-1661 |
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| creator | Yoon, Se-Jin Wills, Andrea E Chuong, Edward Gupta, Rakhi Baker, Julie C |
| description | Nodal signaling, mediated through SMAD transcription factors, is necessary for pluripotency maintenance and endoderm commitment. We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. We demonstrate that two basic helix-loop-helix (bHLH) proteins-HEB and E2A-bind the SCA motif at regions overlapping SMAD2/3 and FOXH1. Furthermore, we show that HEB and E2A associate with SMAD2/3 and FOXH1, suggesting they form a complex at critical target regions. This association is biologically important, as E2A is critical for mesendoderm specification, gastrulation, and Nodal signal transduction in Xenopus tropicalis embryos. Taken together, E proteins are novel Nodal signaling cofactors that associate with SMAD2/3 and FOXH1 and are necessary for mesendoderm differentiation. |
| doi_str_mv | 10.1101/gad.16800511 |
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We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. We demonstrate that two basic helix-loop-helix (bHLH) proteins-HEB and E2A-bind the SCA motif at regions overlapping SMAD2/3 and FOXH1. Furthermore, we show that HEB and E2A associate with SMAD2/3 and FOXH1, suggesting they form a complex at critical target regions. This association is biologically important, as E2A is critical for mesendoderm specification, gastrulation, and Nodal signal transduction in Xenopus tropicalis embryos. Taken together, E proteins are novel Nodal signaling cofactors that associate with SMAD2/3 and FOXH1 and are necessary for mesendoderm differentiation.</description><identifier>ISSN: 0890-9369</identifier><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.16800511</identifier><identifier>PMID: 21828274</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Amino Acid Motifs ; Animals ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Cell Line ; Chromatin Immunoprecipitation ; Embryonic Stem Cells ; Endoderm - metabolism ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - metabolism ; Gastrulation - genetics ; Gene Expression Regulation, Developmental - genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Left-Right Determination Factors - metabolism ; Protein Binding ; Research Paper ; Signal Transduction ; Smad Proteins, Receptor-Regulated - chemistry ; Smad Proteins, Receptor-Regulated - genetics ; Smad Proteins, Receptor-Regulated - metabolism ; Xenopus - embryology ; Xenopus tropicalis</subject><ispartof>Genes & development, 2011-08, Vol.25 (15), p.1654-1661</ispartof><rights>Copyright © 2011 by Cold Spring Harbor Laboratory Press 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-f900e2736b9f51ca51049c2b514270b3a30c6f20b151c2d3f3b3c24c3b8c763f3</citedby><cites>FETCH-LOGICAL-c481t-f900e2736b9f51ca51049c2b514270b3a30c6f20b151c2d3f3b3c24c3b8c763f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182016/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182016/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21828274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoon, Se-Jin</creatorcontrib><creatorcontrib>Wills, Andrea E</creatorcontrib><creatorcontrib>Chuong, Edward</creatorcontrib><creatorcontrib>Gupta, Rakhi</creatorcontrib><creatorcontrib>Baker, Julie C</creatorcontrib><title>HEB and E2A function as SMAD/FOXH1 cofactors</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>Nodal signaling, mediated through SMAD transcription factors, is necessary for pluripotency maintenance and endoderm commitment. We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. We demonstrate that two basic helix-loop-helix (bHLH) proteins-HEB and E2A-bind the SCA motif at regions overlapping SMAD2/3 and FOXH1. Furthermore, we show that HEB and E2A associate with SMAD2/3 and FOXH1, suggesting they form a complex at critical target regions. This association is biologically important, as E2A is critical for mesendoderm specification, gastrulation, and Nodal signal transduction in Xenopus tropicalis embryos. Taken together, E proteins are novel Nodal signaling cofactors that associate with SMAD2/3 and FOXH1 and are necessary for mesendoderm differentiation.</description><subject>Amino Acid Motifs</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Cell Line</subject><subject>Chromatin Immunoprecipitation</subject><subject>Embryonic Stem Cells</subject><subject>Endoderm - metabolism</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Gastrulation - genetics</subject><subject>Gene Expression Regulation, Developmental - genetics</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Left-Right Determination Factors - metabolism</subject><subject>Protein Binding</subject><subject>Research Paper</subject><subject>Signal Transduction</subject><subject>Smad Proteins, Receptor-Regulated - chemistry</subject><subject>Smad Proteins, Receptor-Regulated - genetics</subject><subject>Smad Proteins, Receptor-Regulated - metabolism</subject><subject>Xenopus - embryology</subject><subject>Xenopus tropicalis</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkb1PwzAQxS0EoqWwMaNsLE17ZztOvCCV0lKkog6AxGY5TlyC2rjECRL_PUH9EExMp9P76enePUIuEQaIgMOlzgYoEoAI8Yh0MeIyjHgcH5MuJBJCyYTskDPv3wFAgBCnpEMxoQmNeZf0Z5PbQJdZMKGjwDalqQtXBtoHT4-ju-F08TrDwDirTe0qf05OrF75_GI3e-RlOnkez8L54v5hPJqHhidYh1YC5DRmIpU2QqMjBC4NTSPkNIaUaQZGWAoptirNmGUpM5QbliYmFu3aIzdb302TrvPM5GVd6ZXaVMVaV1_K6UL9VcriTS3dp2JtLkDRGlzvDCr30eS-VuvCm3y10mXuGq8kUCa4RPyXTBIGSJGxluxvSVM576vcHu5BUD9NqLYJtW-ixa9-ZzjA-9ezbySBgJw</recordid><startdate>20110801</startdate><enddate>20110801</enddate><creator>Yoon, Se-Jin</creator><creator>Wills, Andrea E</creator><creator>Chuong, Edward</creator><creator>Gupta, Rakhi</creator><creator>Baker, Julie C</creator><general>Cold Spring Harbor Laboratory Press</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>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20110801</creationdate><title>HEB and E2A function as SMAD/FOXH1 cofactors</title><author>Yoon, Se-Jin ; Wills, Andrea E ; Chuong, Edward ; Gupta, Rakhi ; Baker, Julie C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-f900e2736b9f51ca51049c2b514270b3a30c6f20b151c2d3f3b3c24c3b8c763f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Amino Acid Motifs</topic><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Cell Line</topic><topic>Chromatin Immunoprecipitation</topic><topic>Embryonic Stem Cells</topic><topic>Endoderm - metabolism</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Gastrulation - genetics</topic><topic>Gene Expression Regulation, Developmental - genetics</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Left-Right Determination Factors - metabolism</topic><topic>Protein Binding</topic><topic>Research Paper</topic><topic>Signal Transduction</topic><topic>Smad Proteins, Receptor-Regulated - chemistry</topic><topic>Smad Proteins, Receptor-Regulated - genetics</topic><topic>Smad Proteins, Receptor-Regulated - metabolism</topic><topic>Xenopus - embryology</topic><topic>Xenopus tropicalis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yoon, Se-Jin</creatorcontrib><creatorcontrib>Wills, Andrea E</creatorcontrib><creatorcontrib>Chuong, Edward</creatorcontrib><creatorcontrib>Gupta, Rakhi</creatorcontrib><creatorcontrib>Baker, Julie C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoon, Se-Jin</au><au>Wills, Andrea E</au><au>Chuong, Edward</au><au>Gupta, Rakhi</au><au>Baker, Julie C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HEB and E2A function as SMAD/FOXH1 cofactors</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>2011-08-01</date><risdate>2011</risdate><volume>25</volume><issue>15</issue><spage>1654</spage><epage>1661</epage><pages>1654-1661</pages><issn>0890-9369</issn><eissn>1549-5477</eissn><abstract>Nodal signaling, mediated through SMAD transcription factors, is necessary for pluripotency maintenance and endoderm commitment. We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. We demonstrate that two basic helix-loop-helix (bHLH) proteins-HEB and E2A-bind the SCA motif at regions overlapping SMAD2/3 and FOXH1. Furthermore, we show that HEB and E2A associate with SMAD2/3 and FOXH1, suggesting they form a complex at critical target regions. This association is biologically important, as E2A is critical for mesendoderm specification, gastrulation, and Nodal signal transduction in Xenopus tropicalis embryos. Taken together, E proteins are novel Nodal signaling cofactors that associate with SMAD2/3 and FOXH1 and are necessary for mesendoderm differentiation.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>21828274</pmid><doi>10.1101/gad.16800511</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Motifs Animals Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Cell Line Chromatin Immunoprecipitation Embryonic Stem Cells Endoderm - metabolism Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism Gastrulation - genetics Gene Expression Regulation, Developmental - genetics High-Throughput Nucleotide Sequencing Humans Left-Right Determination Factors - metabolism Protein Binding Research Paper Signal Transduction Smad Proteins, Receptor-Regulated - chemistry Smad Proteins, Receptor-Regulated - genetics Smad Proteins, Receptor-Regulated - metabolism Xenopus - embryology Xenopus tropicalis |
| title | HEB and E2A function as SMAD/FOXH1 cofactors |
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