Gene Dosage–Dependent Embryonic Development and Proliferation Defects in Mice Lacking the Transcriptional Integrator p300
The transcriptional coactivator and integrator p300 and its closely related family member CBP mediate multiple, signal-dependent transcriptional events. We have generated mice lacking a functional p300 gene. Animals nullizygous for p300 died between days 9 and 11.5 of gestation, exhibiting defects i...
Gespeichert in:
| Veröffentlicht in: | Cell 1998-05, Vol.93 (3), p.361-372 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 372 |
|---|---|
| container_issue | 3 |
| container_start_page | 361 |
| container_title | Cell |
| container_volume | 93 |
| creator | Yao, Tso-Pang Oh, Suk P Fuchs, Miriam Zhou, Nai-Dong Ch'ng, Lian-Ee Newsome, David Bronson, Roderick T Li, En Livingston, David M Eckner, Richard |
| description | The transcriptional coactivator and integrator p300 and its closely related family member CBP mediate multiple, signal-dependent transcriptional events. We have generated mice lacking a functional
p300 gene. Animals nullizygous for
p300 died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development. Cells derived from p300-deficient embryos displayed specific transcriptional defects and proliferated poorly. Surprisingly,
p300 heterozygotes also manifested considerable embryonic lethality. Moreover, double heterozygosity for
p300 and
cbp was invariably associated with embryonic death. Thus, mouse development is exquisitely sensitive to the overall gene dosage of
p300 and
cbp. Our results provide genetic evidence that a coactivator endowed with histone acetyltransferase activity is essential for mammalian cell proliferation and development. |
| doi_str_mv | 10.1016/S0092-8674(00)81165-4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_79878672</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0092867400811654</els_id><sourcerecordid>16447884</sourcerecordid><originalsourceid>FETCH-LOGICAL-c492t-695afa8c70ddd6cd6e5943f30a4115fcfd580ed52192fcc13624206faf333db3</originalsourceid><addsrcrecordid>eNqFkcFq3DAQhkVoSLdpHiGgU2kObka2ZFunUrJpEtjSQvcutNJoq9aWXMkbCL30HfqGfZLY2SXXnAbm__4Z-H9Czhl8YMDqy-8AsizauuHvAS5axmpR8COyYCCbgrOmfEUWz8hr8ibnnwDQCiFOyIkUEljDFuTPDQaky5j1Fv___bfEAYPFMNLrfpMeYvCGLvEeuzj081YHS7-l2HmHSY8-hkl1aMZMfaBfvEG60uaXD1s6_kC6Tjpkk_wwk7qjd2HE7eSLiQ4VwFty7HSX8ewwT8n68_X66rZYfb25u_q0KgyX5VjUUminW9OAtbY2tkYheeUq0Jwx4YyzogW0omSydMawqi55CbXTrqoqu6lOybv92SHF3zvMo-p9Nth1OmDcZdXItpkyKl8EWc1507Z8AsUeNCnmnNCpIflepwfFQM3lqKdy1Jy8AlBP5ajZd354sNv0aJ9dhzYm_eNexymNe49JZeMxGLQ-TSErG_0LHx4BXsOg9Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>16447884</pqid></control><display><type>article</type><title>Gene Dosage–Dependent Embryonic Development and Proliferation Defects in Mice Lacking the Transcriptional Integrator p300</title><source>MEDLINE</source><source>Cell Press Free Archives</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Access via ScienceDirect (Elsevier)</source><creator>Yao, Tso-Pang ; Oh, Suk P ; Fuchs, Miriam ; Zhou, Nai-Dong ; Ch'ng, Lian-Ee ; Newsome, David ; Bronson, Roderick T ; Li, En ; Livingston, David M ; Eckner, Richard</creator><creatorcontrib>Yao, Tso-Pang ; Oh, Suk P ; Fuchs, Miriam ; Zhou, Nai-Dong ; Ch'ng, Lian-Ee ; Newsome, David ; Bronson, Roderick T ; Li, En ; Livingston, David M ; Eckner, Richard</creatorcontrib><description>The transcriptional coactivator and integrator p300 and its closely related family member CBP mediate multiple, signal-dependent transcriptional events. We have generated mice lacking a functional
p300 gene. Animals nullizygous for
p300 died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development. Cells derived from p300-deficient embryos displayed specific transcriptional defects and proliferated poorly. Surprisingly,
p300 heterozygotes also manifested considerable embryonic lethality. Moreover, double heterozygosity for
p300 and
cbp was invariably associated with embryonic death. Thus, mouse development is exquisitely sensitive to the overall gene dosage of
p300 and
cbp. Our results provide genetic evidence that a coactivator endowed with histone acetyltransferase activity is essential for mammalian cell proliferation and development.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/S0092-8674(00)81165-4</identifier><identifier>PMID: 9590171</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Brain - abnormalities ; CCAAT-Enhancer-Binding Proteins ; Cell Division ; Cells, Cultured ; Crosses, Genetic ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - physiology ; Embryonic and Fetal Development - genetics ; Fibroblasts - cytology ; Gene Dosage ; Gene Expression Regulation, Developmental - physiology ; Heart - embryology ; Heterozygote ; Histone Acetyltransferases ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neural Tube Defects - genetics ; Nuclear Proteins - genetics ; Nuclear Proteins - physiology ; Nuclear Receptor Coactivator 3 ; Receptors, Retinoic Acid - genetics ; Trans-Activators - genetics ; Trans-Activators - physiology ; Transcription, Genetic</subject><ispartof>Cell, 1998-05, Vol.93 (3), p.361-372</ispartof><rights>1998 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-695afa8c70ddd6cd6e5943f30a4115fcfd580ed52192fcc13624206faf333db3</citedby><cites>FETCH-LOGICAL-c492t-695afa8c70ddd6cd6e5943f30a4115fcfd580ed52192fcc13624206faf333db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0092-8674(00)81165-4$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9590171$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yao, Tso-Pang</creatorcontrib><creatorcontrib>Oh, Suk P</creatorcontrib><creatorcontrib>Fuchs, Miriam</creatorcontrib><creatorcontrib>Zhou, Nai-Dong</creatorcontrib><creatorcontrib>Ch'ng, Lian-Ee</creatorcontrib><creatorcontrib>Newsome, David</creatorcontrib><creatorcontrib>Bronson, Roderick T</creatorcontrib><creatorcontrib>Li, En</creatorcontrib><creatorcontrib>Livingston, David M</creatorcontrib><creatorcontrib>Eckner, Richard</creatorcontrib><title>Gene Dosage–Dependent Embryonic Development and Proliferation Defects in Mice Lacking the Transcriptional Integrator p300</title><title>Cell</title><addtitle>Cell</addtitle><description>The transcriptional coactivator and integrator p300 and its closely related family member CBP mediate multiple, signal-dependent transcriptional events. We have generated mice lacking a functional
p300 gene. Animals nullizygous for
p300 died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development. Cells derived from p300-deficient embryos displayed specific transcriptional defects and proliferated poorly. Surprisingly,
p300 heterozygotes also manifested considerable embryonic lethality. Moreover, double heterozygosity for
p300 and
cbp was invariably associated with embryonic death. Thus, mouse development is exquisitely sensitive to the overall gene dosage of
p300 and
cbp. Our results provide genetic evidence that a coactivator endowed with histone acetyltransferase activity is essential for mammalian cell proliferation and development.</description><subject>Animals</subject><subject>Brain - abnormalities</subject><subject>CCAAT-Enhancer-Binding Proteins</subject><subject>Cell Division</subject><subject>Cells, Cultured</subject><subject>Crosses, Genetic</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - physiology</subject><subject>Embryonic and Fetal Development - genetics</subject><subject>Fibroblasts - cytology</subject><subject>Gene Dosage</subject><subject>Gene Expression Regulation, Developmental - physiology</subject><subject>Heart - embryology</subject><subject>Heterozygote</subject><subject>Histone Acetyltransferases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Neural Tube Defects - genetics</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - physiology</subject><subject>Nuclear Receptor Coactivator 3</subject><subject>Receptors, Retinoic Acid - genetics</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - physiology</subject><subject>Transcription, Genetic</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFq3DAQhkVoSLdpHiGgU2kObka2ZFunUrJpEtjSQvcutNJoq9aWXMkbCL30HfqGfZLY2SXXnAbm__4Z-H9Czhl8YMDqy-8AsizauuHvAS5axmpR8COyYCCbgrOmfEUWz8hr8ibnnwDQCiFOyIkUEljDFuTPDQaky5j1Fv___bfEAYPFMNLrfpMeYvCGLvEeuzj081YHS7-l2HmHSY8-hkl1aMZMfaBfvEG60uaXD1s6_kC6Tjpkk_wwk7qjd2HE7eSLiQ4VwFty7HSX8ewwT8n68_X66rZYfb25u_q0KgyX5VjUUminW9OAtbY2tkYheeUq0Jwx4YyzogW0omSydMawqi55CbXTrqoqu6lOybv92SHF3zvMo-p9Nth1OmDcZdXItpkyKl8EWc1507Z8AsUeNCnmnNCpIflepwfFQM3lqKdy1Jy8AlBP5ajZd354sNv0aJ9dhzYm_eNexymNe49JZeMxGLQ-TSErG_0LHx4BXsOg9Q</recordid><startdate>19980501</startdate><enddate>19980501</enddate><creator>Yao, Tso-Pang</creator><creator>Oh, Suk P</creator><creator>Fuchs, Miriam</creator><creator>Zhou, Nai-Dong</creator><creator>Ch'ng, Lian-Ee</creator><creator>Newsome, David</creator><creator>Bronson, Roderick T</creator><creator>Li, En</creator><creator>Livingston, David M</creator><creator>Eckner, Richard</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19980501</creationdate><title>Gene Dosage–Dependent Embryonic Development and Proliferation Defects in Mice Lacking the Transcriptional Integrator p300</title><author>Yao, Tso-Pang ; Oh, Suk P ; Fuchs, Miriam ; Zhou, Nai-Dong ; Ch'ng, Lian-Ee ; Newsome, David ; Bronson, Roderick T ; Li, En ; Livingston, David M ; Eckner, Richard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-695afa8c70ddd6cd6e5943f30a4115fcfd580ed52192fcc13624206faf333db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Brain - abnormalities</topic><topic>CCAAT-Enhancer-Binding Proteins</topic><topic>Cell Division</topic><topic>Cells, Cultured</topic><topic>Crosses, Genetic</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - physiology</topic><topic>Embryonic and Fetal Development - genetics</topic><topic>Fibroblasts - cytology</topic><topic>Gene Dosage</topic><topic>Gene Expression Regulation, Developmental - physiology</topic><topic>Heart - embryology</topic><topic>Heterozygote</topic><topic>Histone Acetyltransferases</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Neural Tube Defects - genetics</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - physiology</topic><topic>Nuclear Receptor Coactivator 3</topic><topic>Receptors, Retinoic Acid - genetics</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - physiology</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yao, Tso-Pang</creatorcontrib><creatorcontrib>Oh, Suk P</creatorcontrib><creatorcontrib>Fuchs, Miriam</creatorcontrib><creatorcontrib>Zhou, Nai-Dong</creatorcontrib><creatorcontrib>Ch'ng, Lian-Ee</creatorcontrib><creatorcontrib>Newsome, David</creatorcontrib><creatorcontrib>Bronson, Roderick T</creatorcontrib><creatorcontrib>Li, En</creatorcontrib><creatorcontrib>Livingston, David M</creatorcontrib><creatorcontrib>Eckner, Richard</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yao, Tso-Pang</au><au>Oh, Suk P</au><au>Fuchs, Miriam</au><au>Zhou, Nai-Dong</au><au>Ch'ng, Lian-Ee</au><au>Newsome, David</au><au>Bronson, Roderick T</au><au>Li, En</au><au>Livingston, David M</au><au>Eckner, Richard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene Dosage–Dependent Embryonic Development and Proliferation Defects in Mice Lacking the Transcriptional Integrator p300</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>1998-05-01</date><risdate>1998</risdate><volume>93</volume><issue>3</issue><spage>361</spage><epage>372</epage><pages>361-372</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>The transcriptional coactivator and integrator p300 and its closely related family member CBP mediate multiple, signal-dependent transcriptional events. We have generated mice lacking a functional
p300 gene. Animals nullizygous for
p300 died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development. Cells derived from p300-deficient embryos displayed specific transcriptional defects and proliferated poorly. Surprisingly,
p300 heterozygotes also manifested considerable embryonic lethality. Moreover, double heterozygosity for
p300 and
cbp was invariably associated with embryonic death. Thus, mouse development is exquisitely sensitive to the overall gene dosage of
p300 and
cbp. Our results provide genetic evidence that a coactivator endowed with histone acetyltransferase activity is essential for mammalian cell proliferation and development.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>9590171</pmid><doi>10.1016/S0092-8674(00)81165-4</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0092-8674 |
| ispartof | Cell, 1998-05, Vol.93 (3), p.361-372 |
| issn | 0092-8674 1097-4172 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_79878672 |
| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via ScienceDirect (Elsevier) |
| subjects | Animals Brain - abnormalities CCAAT-Enhancer-Binding Proteins Cell Division Cells, Cultured Crosses, Genetic DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Embryonic and Fetal Development - genetics Fibroblasts - cytology Gene Dosage Gene Expression Regulation, Developmental - physiology Heart - embryology Heterozygote Histone Acetyltransferases Mice Mice, Inbred C57BL Mice, Knockout Neural Tube Defects - genetics Nuclear Proteins - genetics Nuclear Proteins - physiology Nuclear Receptor Coactivator 3 Receptors, Retinoic Acid - genetics Trans-Activators - genetics Trans-Activators - physiology Transcription, Genetic |
| title | Gene Dosage–Dependent Embryonic Development and Proliferation Defects in Mice Lacking the Transcriptional Integrator p300 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T07%3A18%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Gene%20Dosage%E2%80%93Dependent%20Embryonic%20Development%20and%20Proliferation%20Defects%20in%20Mice%20Lacking%20the%20Transcriptional%20Integrator%20p300&rft.jtitle=Cell&rft.au=Yao,%20Tso-Pang&rft.date=1998-05-01&rft.volume=93&rft.issue=3&rft.spage=361&rft.epage=372&rft.pages=361-372&rft.issn=0092-8674&rft.eissn=1097-4172&rft_id=info:doi/10.1016/S0092-8674(00)81165-4&rft_dat=%3Cproquest_cross%3E16447884%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=16447884&rft_id=info:pmid/9590171&rft_els_id=S0092867400811654&rfr_iscdi=true |