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The Role of PTIP in Maintaining Embryonic Stem Cell Pluripotency
Pax transactivation domain‐interacting protein (PTIP) is a ubiquitously expressed, nuclear protein that is part of a histone H3K4 methyltransferase complex and is essential for embryonic development. Methylation of H3K4 is an epigenetic mark found on many critical developmental regulatory genes in e...
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| Published in: | Stem cells (Dayton, Ohio) Ohio), 2009-07, Vol.27 (7), p.1516-1523 |
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| container_end_page | 1523 |
| container_issue | 7 |
| container_start_page | 1516 |
| container_title | Stem cells (Dayton, Ohio) |
| container_volume | 27 |
| creator | Kim, Doyeob Patel, Sanjeevkumar R. Xiao, Hong Dressler, Gregory R. |
| description | Pax transactivation domain‐interacting protein (PTIP) is a ubiquitously expressed, nuclear protein that is part of a histone H3K4 methyltransferase complex and is essential for embryonic development. Methylation of H3K4 is an epigenetic mark found on many critical developmental regulatory genes in embryonic stem (ES) cells and, together with H3K27 methylation, constitutes a bivalent epigenetic signature. To address the function of PTIP in ES cells, we generated ES cell lines from a floxed ptip allele and deleted PTIP function with Cre recombinase. The ptip−/− ES cell lines exhibited a high degree of spontaneous differentiation to trophectoderm and a loss of pluripotency. Reduced levels of Oct4 expression and H3K4 methylation were observed. Upon differentiation, ptip−/− embryoid bodies showed reduced levels of marker gene expression for all three primary germ layers. These results suggest that the maintenance of H3K4 methylation is essential and requires PTIP function during the in vitro propagation of pluripotent ES cells. STEM CELLS 2009;27:1516–1523 |
| doi_str_mv | 10.1002/stem.79 |
| format | article |
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Methylation of H3K4 is an epigenetic mark found on many critical developmental regulatory genes in embryonic stem (ES) cells and, together with H3K27 methylation, constitutes a bivalent epigenetic signature. To address the function of PTIP in ES cells, we generated ES cell lines from a floxed ptip allele and deleted PTIP function with Cre recombinase. The ptip−/− ES cell lines exhibited a high degree of spontaneous differentiation to trophectoderm and a loss of pluripotency. Reduced levels of Oct4 expression and H3K4 methylation were observed. Upon differentiation, ptip−/− embryoid bodies showed reduced levels of marker gene expression for all three primary germ layers. These results suggest that the maintenance of H3K4 methylation is essential and requires PTIP function during the in vitro propagation of pluripotent ES cells. 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Methylation of H3K4 is an epigenetic mark found on many critical developmental regulatory genes in embryonic stem (ES) cells and, together with H3K27 methylation, constitutes a bivalent epigenetic signature. To address the function of PTIP in ES cells, we generated ES cell lines from a floxed ptip allele and deleted PTIP function with Cre recombinase. The ptip−/− ES cell lines exhibited a high degree of spontaneous differentiation to trophectoderm and a loss of pluripotency. Reduced levels of Oct4 expression and H3K4 methylation were observed. Upon differentiation, ptip−/− embryoid bodies showed reduced levels of marker gene expression for all three primary germ layers. These results suggest that the maintenance of H3K4 methylation is essential and requires PTIP function during the in vitro propagation of pluripotent ES cells. STEM CELLS 2009;27:1516–1523</description><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - physiology</subject><subject>Blotting, Western</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - physiology</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Chromatin Immunoprecipitation</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Histones - metabolism</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Methylation</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - physiology</subject><subject>Oct4</subject><subject>Octamer Transcription Factor-3 - genetics</subject><subject>Octamer Transcription Factor-3 - physiology</subject><subject>Pluripotent Stem Cells - cytology</subject><subject>Pluripotent Stem Cells - metabolism</subject><subject>PTIP</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Spontaneous differentiation</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNp1kE1LAzEQhoMotlbxH0hOepCtyW5mk9yUUj-gxWLXc8huE43sR012kf33bmnBk4fhncPDM8OL0CUlU0pIfBdaU025PEJjCkxGTFJxPOwkTSMgUo7QWQhfhFAGQpyiEZXAGEvZGN1nnwa_NaXBjcWr7GWFXY2X2tXtMK7-wPMq931TuwKvhxt4ZsoSr8rOu23Tmrroz9GJ1WUwF4ecoPfHeTZ7jhavTy-zh0VUJEzIKOdxzonUSRqnsCEURAIstixPoTA25syAiLm0OhEk2RBIuAXQVhcWWE4MJBN0vfduffPdmdCqyoVi-EbXpumCSjkAEXQH3uzBwjcheGPV1rtK-15RonZlqV1ZisuBvDoou7wymz_u0M4A3O6BH1ea_j-PWmfz5aD7BT-1cW4</recordid><startdate>200907</startdate><enddate>200907</enddate><creator>Kim, Doyeob</creator><creator>Patel, Sanjeevkumar R.</creator><creator>Xiao, Hong</creator><creator>Dressler, Gregory R.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</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></search><sort><creationdate>200907</creationdate><title>The Role of PTIP in Maintaining Embryonic Stem Cell Pluripotency</title><author>Kim, Doyeob ; Patel, Sanjeevkumar R. ; Xiao, Hong ; Dressler, Gregory R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3489-b72b709a36265d01583542f4b65cef274e58279fa3803d0537f55afacf54b0e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - physiology</topic><topic>Blotting, Western</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - physiology</topic><topic>Cell Differentiation</topic><topic>Cells, Cultured</topic><topic>Chromatin Immunoprecipitation</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Histones - metabolism</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Methylation</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - physiology</topic><topic>Oct4</topic><topic>Octamer Transcription Factor-3 - genetics</topic><topic>Octamer Transcription Factor-3 - physiology</topic><topic>Pluripotent Stem Cells - cytology</topic><topic>Pluripotent Stem Cells - metabolism</topic><topic>PTIP</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Spontaneous differentiation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Doyeob</creatorcontrib><creatorcontrib>Patel, Sanjeevkumar R.</creatorcontrib><creatorcontrib>Xiao, Hong</creatorcontrib><creatorcontrib>Dressler, Gregory R.</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><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Doyeob</au><au>Patel, Sanjeevkumar R.</au><au>Xiao, Hong</au><au>Dressler, Gregory R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Role of PTIP in Maintaining Embryonic Stem Cell Pluripotency</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>2009-07</date><risdate>2009</risdate><volume>27</volume><issue>7</issue><spage>1516</spage><epage>1523</epage><pages>1516-1523</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>Pax transactivation domain‐interacting protein (PTIP) is a ubiquitously expressed, nuclear protein that is part of a histone H3K4 methyltransferase complex and is essential for embryonic development. Methylation of H3K4 is an epigenetic mark found on many critical developmental regulatory genes in embryonic stem (ES) cells and, together with H3K27 methylation, constitutes a bivalent epigenetic signature. To address the function of PTIP in ES cells, we generated ES cell lines from a floxed ptip allele and deleted PTIP function with Cre recombinase. The ptip−/− ES cell lines exhibited a high degree of spontaneous differentiation to trophectoderm and a loss of pluripotency. Reduced levels of Oct4 expression and H3K4 methylation were observed. Upon differentiation, ptip−/− embryoid bodies showed reduced levels of marker gene expression for all three primary germ layers. These results suggest that the maintenance of H3K4 methylation is essential and requires PTIP function during the in vitro propagation of pluripotent ES cells. STEM CELLS 2009;27:1516–1523</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19544464</pmid><doi>10.1002/stem.79</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press:Jisc Collections:OUP Read and Publish 2024-2025 (2024 collection) (Reading list) |
| subjects | Animals Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - physiology Blotting, Western Carrier Proteins - genetics Carrier Proteins - physiology Cell Differentiation Cells, Cultured Chromatin Immunoprecipitation Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Epigenetics Female Histones - metabolism Immunohistochemistry Male Methylation Mice Mice, Mutant Strains Nuclear Proteins - genetics Nuclear Proteins - physiology Oct4 Octamer Transcription Factor-3 - genetics Octamer Transcription Factor-3 - physiology Pluripotent Stem Cells - cytology Pluripotent Stem Cells - metabolism PTIP Reverse Transcriptase Polymerase Chain Reaction Spontaneous differentiation |
| title | The Role of PTIP in Maintaining Embryonic Stem Cell Pluripotency |
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