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Role of BRD4 in hematopoietic differentiation of embryonic stem cells
The bromodomain and extra terminal (BET) protein family member BRD4 is a transcriptional regulator, critical for cell cycle progression and cellular viability. Here, we show that BRD4 plays an important role in embryonic stem cell (ESC) regulation. During differentiation of ESCs, BRD4 expression is...
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| Published in: | Epigenetics 2014-04, Vol.9 (4), p.566-578 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Article |
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| container_end_page | 578 |
| container_issue | 4 |
| container_start_page | 566 |
| container_title | Epigenetics |
| container_volume | 9 |
| creator | Rodriguez, Ramon M Suarez-Alvarez, Beatriz Salvanés, Ruben Huidobro, Covadonga Toraño, Estela G Garcia-Perez, Jose L Lopez-Larrea, Carlos Fernandez, Agustin F Bueno, Clara Menendez, Pablo Fraga, Mario F |
| description | The bromodomain and extra terminal (BET) protein family member BRD4 is a transcriptional regulator, critical for cell cycle progression and cellular viability. Here, we show that BRD4 plays an important role in embryonic stem cell (ESC) regulation. During differentiation of ESCs, BRD4 expression is upregulated and its gene promoter becomes demethylated. Disruption of BRD4 expression in ESCs did not induce spontaneous differentiation but severely diminished hematoendothelial potential. Although BRD4 regulates c-Myc expression, our data show that the role of BRD4 in hematopoietic commitment is not exclusively mediated by c-Myc. Our results indicate that BRD4 is epigenetically regulated during hematopoietic differentiation ESCs in the context of a still unknown signaling pathway. |
| doi_str_mv | 10.4161/epi.27711 |
| format | article |
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Here, we show that BRD4 plays an important role in embryonic stem cell (ESC) regulation. During differentiation of ESCs, BRD4 expression is upregulated and its gene promoter becomes demethylated. Disruption of BRD4 expression in ESCs did not induce spontaneous differentiation but severely diminished hematoendothelial potential. Although BRD4 regulates c-Myc expression, our data show that the role of BRD4 in hematopoietic commitment is not exclusively mediated by c-Myc. Our results indicate that BRD4 is epigenetically regulated during hematopoietic differentiation ESCs in the context of a still unknown signaling pathway.</description><identifier>ISSN: 1559-2294</identifier><identifier>EISSN: 1559-2308</identifier><identifier>DOI: 10.4161/epi.27711</identifier><identifier>PMID: 24445267</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>BRD4 ; bromodomain ; Cell Differentiation ; Cell Line ; differentiation ; DNA Methylation ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Epigenesis, Genetic ; Fetal Blood - cytology ; Hematopoiesis ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - metabolism ; Humans ; Infant, Newborn ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Proto-Oncogene Proteins c-myc - genetics ; Proto-Oncogene Proteins c-myc - metabolism ; Research Paper ; Signal Transduction ; stem cells ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>Epigenetics, 2014-04, Vol.9 (4), p.566-578</ispartof><rights>Copyright © 2014 Landes Bioscience 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-be3cd0c50d0b8d83a9b73aa2640712df96398caeed432877b67878ba9698ee2f3</citedby><cites>FETCH-LOGICAL-c420t-be3cd0c50d0b8d83a9b73aa2640712df96398caeed432877b67878ba9698ee2f3</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/PMC4121367/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121367/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24445267$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rodriguez, Ramon M</creatorcontrib><creatorcontrib>Suarez-Alvarez, Beatriz</creatorcontrib><creatorcontrib>Salvanés, Ruben</creatorcontrib><creatorcontrib>Huidobro, Covadonga</creatorcontrib><creatorcontrib>Toraño, Estela G</creatorcontrib><creatorcontrib>Garcia-Perez, Jose L</creatorcontrib><creatorcontrib>Lopez-Larrea, Carlos</creatorcontrib><creatorcontrib>Fernandez, Agustin F</creatorcontrib><creatorcontrib>Bueno, Clara</creatorcontrib><creatorcontrib>Menendez, Pablo</creatorcontrib><creatorcontrib>Fraga, Mario F</creatorcontrib><title>Role of BRD4 in hematopoietic differentiation of embryonic stem cells</title><title>Epigenetics</title><addtitle>Epigenetics</addtitle><description>The bromodomain and extra terminal (BET) protein family member BRD4 is a transcriptional regulator, critical for cell cycle progression and cellular viability. Here, we show that BRD4 plays an important role in embryonic stem cell (ESC) regulation. During differentiation of ESCs, BRD4 expression is upregulated and its gene promoter becomes demethylated. Disruption of BRD4 expression in ESCs did not induce spontaneous differentiation but severely diminished hematoendothelial potential. Although BRD4 regulates c-Myc expression, our data show that the role of BRD4 in hematopoietic commitment is not exclusively mediated by c-Myc. Our results indicate that BRD4 is epigenetically regulated during hematopoietic differentiation ESCs in the context of a still unknown signaling pathway.</description><subject>BRD4</subject><subject>bromodomain</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>differentiation</subject><subject>DNA Methylation</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Epigenesis, Genetic</subject><subject>Fetal Blood - cytology</subject><subject>Hematopoiesis</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>Proto-Oncogene Proteins c-myc - metabolism</subject><subject>Research Paper</subject><subject>Signal Transduction</subject><subject>stem cells</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>1559-2294</issn><issn>1559-2308</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNplkElLBDEQhYMo7gf_gPRRD6PZOstFcBkXGBAGPYd0uqKR7s6Y9Cjz7-1xVBRPVfA-Xr16CB0QfMKJIKcwCydUSkLW0DYpSz2iDKv1751qvoV2cn7BmDOh9Sbaopzzkgq5jcbT2EARfXExveJF6IpnaG0fZzFAH1xRB-8hQdcH24fYLUFoq7SI3SDmHtrCQdPkPbThbZNh_2vuosfr8cPl7Whyf3N3eT4ZOU5xP6qAuRq7Ete4UrViVleSWUsFx5LQ2mvBtHIWoOaMKikrIZVUldVCKwDq2S46W_nO5lULtRuCJduYWQqtTQsTbTB_lS48m6f4ZjihhAk5GBx9GaT4Oofcmzbk5Qu2gzjPhpREKsUUFwN6vEJdijkn8D9nCDbL2s1Qu_msfWAPf-f6Ib97HgC-AkLnY2rte0xNbXq7aGLyyXYuZMP--34AaM6QqQ</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Rodriguez, Ramon M</creator><creator>Suarez-Alvarez, Beatriz</creator><creator>Salvanés, Ruben</creator><creator>Huidobro, Covadonga</creator><creator>Toraño, Estela G</creator><creator>Garcia-Perez, Jose L</creator><creator>Lopez-Larrea, Carlos</creator><creator>Fernandez, Agustin F</creator><creator>Bueno, Clara</creator><creator>Menendez, Pablo</creator><creator>Fraga, Mario F</creator><general>Taylor & Francis</general><general>Landes Bioscience</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>5PM</scope></search><sort><creationdate>20140401</creationdate><title>Role of BRD4 in hematopoietic differentiation of embryonic stem cells</title><author>Rodriguez, Ramon M ; Suarez-Alvarez, Beatriz ; Salvanés, Ruben ; Huidobro, Covadonga ; Toraño, Estela G ; Garcia-Perez, Jose L ; Lopez-Larrea, Carlos ; Fernandez, Agustin F ; Bueno, Clara ; Menendez, Pablo ; Fraga, Mario F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-be3cd0c50d0b8d83a9b73aa2640712df96398caeed432877b67878ba9698ee2f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>BRD4</topic><topic>bromodomain</topic><topic>Cell Differentiation</topic><topic>Cell Line</topic><topic>differentiation</topic><topic>DNA Methylation</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Epigenesis, Genetic</topic><topic>Fetal Blood - cytology</topic><topic>Hematopoiesis</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>Proto-Oncogene Proteins c-myc - metabolism</topic><topic>Research Paper</topic><topic>Signal Transduction</topic><topic>stem cells</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rodriguez, Ramon M</creatorcontrib><creatorcontrib>Suarez-Alvarez, Beatriz</creatorcontrib><creatorcontrib>Salvanés, Ruben</creatorcontrib><creatorcontrib>Huidobro, Covadonga</creatorcontrib><creatorcontrib>Toraño, Estela G</creatorcontrib><creatorcontrib>Garcia-Perez, Jose L</creatorcontrib><creatorcontrib>Lopez-Larrea, Carlos</creatorcontrib><creatorcontrib>Fernandez, Agustin F</creatorcontrib><creatorcontrib>Bueno, Clara</creatorcontrib><creatorcontrib>Menendez, Pablo</creatorcontrib><creatorcontrib>Fraga, Mario F</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>PubMed Central (Full Participant titles)</collection><jtitle>Epigenetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rodriguez, Ramon M</au><au>Suarez-Alvarez, Beatriz</au><au>Salvanés, Ruben</au><au>Huidobro, Covadonga</au><au>Toraño, Estela G</au><au>Garcia-Perez, Jose L</au><au>Lopez-Larrea, Carlos</au><au>Fernandez, Agustin F</au><au>Bueno, Clara</au><au>Menendez, Pablo</au><au>Fraga, Mario F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of BRD4 in hematopoietic differentiation of embryonic stem cells</atitle><jtitle>Epigenetics</jtitle><addtitle>Epigenetics</addtitle><date>2014-04-01</date><risdate>2014</risdate><volume>9</volume><issue>4</issue><spage>566</spage><epage>578</epage><pages>566-578</pages><issn>1559-2294</issn><eissn>1559-2308</eissn><abstract>The bromodomain and extra terminal (BET) protein family member BRD4 is a transcriptional regulator, critical for cell cycle progression and cellular viability. 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| subjects | BRD4 bromodomain Cell Differentiation Cell Line differentiation DNA Methylation Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Epigenesis, Genetic Fetal Blood - cytology Hematopoiesis Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Humans Infant, Newborn Nuclear Proteins - genetics Nuclear Proteins - metabolism Proto-Oncogene Proteins c-myc - genetics Proto-Oncogene Proteins c-myc - metabolism Research Paper Signal Transduction stem cells Transcription Factors - genetics Transcription Factors - metabolism |
| title | Role of BRD4 in hematopoietic differentiation of embryonic stem cells |
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