Collapse of the hepatic gene regulatory network in the absence of FoxA factors
The FoxA transcription factors are critical for liver development through their pioneering activity, which initiates a highly complex regulatory network thought to become progressively resistant to the loss of any individual hepatic transcription factor via mutual redundancy. To investigate the disp...
Gespeichert in:
| Veröffentlicht in: | Genes & development 2020-08, Vol.34 (15-16), p.1039-1050 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1050 |
|---|---|
| container_issue | 15-16 |
| container_start_page | 1039 |
| container_title | Genes & development |
| container_volume | 34 |
| creator | Reizel, Yitzhak Morgan, Ashleigh Gao, Long Lan, Yemin Manduchi, Elisabetta Waite, Eric L Wang, Amber W Wells, Andrew Kaestner, Klaus H |
| description | The FoxA transcription factors are critical for liver development through their pioneering activity, which initiates a highly complex regulatory network thought to become progressively resistant to the loss of any individual hepatic transcription factor via mutual redundancy. To investigate the dispensability of FoxA factors for maintaining this regulatory network, we ablated all FoxA genes in the adult mouse liver. Remarkably, loss of FoxA caused rapid and massive reduction in the expression of critical liver genes. Activity of these genes was reduced back to the low levels of the fetal prehepatic endoderm stage, leading to necrosis and lethality within days. Mechanistically, we found FoxA proteins to be required for maintaining enhancer activity, chromatin accessibility, nucleosome positioning, and binding of HNF4α. Thus, the FoxA factors act continuously, guarding hepatic enhancer activity throughout adult life. |
| doi_str_mv | 10.1101/gad.337691.120 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7397852</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>32561546</sourcerecordid><originalsourceid>FETCH-LOGICAL-c493t-dce3e0c6e000d363b3b04e52abc3bf085d4176adfa188fbb5ee4c93269e150b73</originalsourceid><addsrcrecordid>eNpVkLFOwzAQhi0EoqWwMiK_QIIdx068IFUVBaQKFpgt27mkgTSu7BTo22NaqGC64b7_v9OH0CUlKaWEXje6ShkrhKQpzcgRGlOey4TnRXGMxqSUJJFMyBE6C-GVECKIEKdoxDIuIijG6HHmuk6vA2BX42EJeAlrPbQWN9AD9tBsOj04v8U9DB_Ov-G232HaBOjtLjV3n1NcaxuxcI5Oat0FuPiZE_Qyv32e3SeLp7uH2XSR2FyyIaksMCBWQHypYoIZZkgOPNPGMlOTklc5LYSuak3LsjaGA-RWskxIoJyYgk3Qzb53vTEriHX94HWn1r5dab9VTrfq_6Zvl6px76pgsih5FgvSfYH1LgQP9SFLifo2q6JZtTerotkYuPp78YD_qmRfiL12jA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Collapse of the hepatic gene regulatory network in the absence of FoxA factors</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Reizel, Yitzhak ; Morgan, Ashleigh ; Gao, Long ; Lan, Yemin ; Manduchi, Elisabetta ; Waite, Eric L ; Wang, Amber W ; Wells, Andrew ; Kaestner, Klaus H</creator><creatorcontrib>Reizel, Yitzhak ; Morgan, Ashleigh ; Gao, Long ; Lan, Yemin ; Manduchi, Elisabetta ; Waite, Eric L ; Wang, Amber W ; Wells, Andrew ; Kaestner, Klaus H</creatorcontrib><description>The FoxA transcription factors are critical for liver development through their pioneering activity, which initiates a highly complex regulatory network thought to become progressively resistant to the loss of any individual hepatic transcription factor via mutual redundancy. To investigate the dispensability of FoxA factors for maintaining this regulatory network, we ablated all FoxA genes in the adult mouse liver. Remarkably, loss of FoxA caused rapid and massive reduction in the expression of critical liver genes. Activity of these genes was reduced back to the low levels of the fetal prehepatic endoderm stage, leading to necrosis and lethality within days. Mechanistically, we found FoxA proteins to be required for maintaining enhancer activity, chromatin accessibility, nucleosome positioning, and binding of HNF4α. Thus, the FoxA factors act continuously, guarding hepatic enhancer activity throughout adult life.</description><identifier>ISSN: 0890-9369</identifier><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.337691.120</identifier><identifier>PMID: 32561546</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Animals ; Binding Sites ; Chromatin - metabolism ; Enhancer Elements, Genetic ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - metabolism ; Forkhead Transcription Factors - physiology ; Gene Expression Regulation ; Gene Knockdown Techniques ; Gene Regulatory Networks ; Hepatocyte Nuclear Factor 3-alpha - genetics ; Hepatocyte Nuclear Factor 3-beta - genetics ; Hepatocyte Nuclear Factor 3-gamma - genetics ; Hepatocyte Nuclear Factor 4 - metabolism ; Liver - metabolism ; Liver - pathology ; Liver Failure - etiology ; Liver Failure - pathology ; Male ; Mice ; Nucleosomes ; Research Paper</subject><ispartof>Genes & development, 2020-08, Vol.34 (15-16), p.1039-1050</ispartof><rights>2020 Reizel et al.; Published by Cold Spring Harbor Laboratory Press.</rights><rights>2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-dce3e0c6e000d363b3b04e52abc3bf085d4176adfa188fbb5ee4c93269e150b73</citedby><cites>FETCH-LOGICAL-c493t-dce3e0c6e000d363b3b04e52abc3bf085d4176adfa188fbb5ee4c93269e150b73</cites><orcidid>0000-0002-1228-021X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397852/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397852/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27915,27916,53782,53784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32561546$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reizel, Yitzhak</creatorcontrib><creatorcontrib>Morgan, Ashleigh</creatorcontrib><creatorcontrib>Gao, Long</creatorcontrib><creatorcontrib>Lan, Yemin</creatorcontrib><creatorcontrib>Manduchi, Elisabetta</creatorcontrib><creatorcontrib>Waite, Eric L</creatorcontrib><creatorcontrib>Wang, Amber W</creatorcontrib><creatorcontrib>Wells, Andrew</creatorcontrib><creatorcontrib>Kaestner, Klaus H</creatorcontrib><title>Collapse of the hepatic gene regulatory network in the absence of FoxA factors</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>The FoxA transcription factors are critical for liver development through their pioneering activity, which initiates a highly complex regulatory network thought to become progressively resistant to the loss of any individual hepatic transcription factor via mutual redundancy. To investigate the dispensability of FoxA factors for maintaining this regulatory network, we ablated all FoxA genes in the adult mouse liver. Remarkably, loss of FoxA caused rapid and massive reduction in the expression of critical liver genes. Activity of these genes was reduced back to the low levels of the fetal prehepatic endoderm stage, leading to necrosis and lethality within days. Mechanistically, we found FoxA proteins to be required for maintaining enhancer activity, chromatin accessibility, nucleosome positioning, and binding of HNF4α. Thus, the FoxA factors act continuously, guarding hepatic enhancer activity throughout adult life.</description><subject>Animals</subject><subject>Binding Sites</subject><subject>Chromatin - metabolism</subject><subject>Enhancer Elements, Genetic</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Forkhead Transcription Factors - physiology</subject><subject>Gene Expression Regulation</subject><subject>Gene Knockdown Techniques</subject><subject>Gene Regulatory Networks</subject><subject>Hepatocyte Nuclear Factor 3-alpha - genetics</subject><subject>Hepatocyte Nuclear Factor 3-beta - genetics</subject><subject>Hepatocyte Nuclear Factor 3-gamma - genetics</subject><subject>Hepatocyte Nuclear Factor 4 - metabolism</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver Failure - etiology</subject><subject>Liver Failure - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Nucleosomes</subject><subject>Research Paper</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkLFOwzAQhi0EoqWwMiK_QIIdx068IFUVBaQKFpgt27mkgTSu7BTo22NaqGC64b7_v9OH0CUlKaWEXje6ShkrhKQpzcgRGlOey4TnRXGMxqSUJJFMyBE6C-GVECKIEKdoxDIuIijG6HHmuk6vA2BX42EJeAlrPbQWN9AD9tBsOj04v8U9DB_Ov-G232HaBOjtLjV3n1NcaxuxcI5Oat0FuPiZE_Qyv32e3SeLp7uH2XSR2FyyIaksMCBWQHypYoIZZkgOPNPGMlOTklc5LYSuak3LsjaGA-RWskxIoJyYgk3Qzb53vTEriHX94HWn1r5dab9VTrfq_6Zvl6px76pgsih5FgvSfYH1LgQP9SFLifo2q6JZtTerotkYuPp78YD_qmRfiL12jA</recordid><startdate>20200801</startdate><enddate>20200801</enddate><creator>Reizel, Yitzhak</creator><creator>Morgan, Ashleigh</creator><creator>Gao, Long</creator><creator>Lan, Yemin</creator><creator>Manduchi, Elisabetta</creator><creator>Waite, Eric L</creator><creator>Wang, Amber W</creator><creator>Wells, Andrew</creator><creator>Kaestner, Klaus H</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>5PM</scope><orcidid>https://orcid.org/0000-0002-1228-021X</orcidid></search><sort><creationdate>20200801</creationdate><title>Collapse of the hepatic gene regulatory network in the absence of FoxA factors</title><author>Reizel, Yitzhak ; Morgan, Ashleigh ; Gao, Long ; Lan, Yemin ; Manduchi, Elisabetta ; Waite, Eric L ; Wang, Amber W ; Wells, Andrew ; Kaestner, Klaus H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-dce3e0c6e000d363b3b04e52abc3bf085d4176adfa188fbb5ee4c93269e150b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Binding Sites</topic><topic>Chromatin - metabolism</topic><topic>Enhancer Elements, Genetic</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Forkhead Transcription Factors - physiology</topic><topic>Gene Expression Regulation</topic><topic>Gene Knockdown Techniques</topic><topic>Gene Regulatory Networks</topic><topic>Hepatocyte Nuclear Factor 3-alpha - genetics</topic><topic>Hepatocyte Nuclear Factor 3-beta - genetics</topic><topic>Hepatocyte Nuclear Factor 3-gamma - genetics</topic><topic>Hepatocyte Nuclear Factor 4 - metabolism</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver Failure - etiology</topic><topic>Liver Failure - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Nucleosomes</topic><topic>Research Paper</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reizel, Yitzhak</creatorcontrib><creatorcontrib>Morgan, Ashleigh</creatorcontrib><creatorcontrib>Gao, Long</creatorcontrib><creatorcontrib>Lan, Yemin</creatorcontrib><creatorcontrib>Manduchi, Elisabetta</creatorcontrib><creatorcontrib>Waite, Eric L</creatorcontrib><creatorcontrib>Wang, Amber W</creatorcontrib><creatorcontrib>Wells, Andrew</creatorcontrib><creatorcontrib>Kaestner, Klaus H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Reizel, Yitzhak</au><au>Morgan, Ashleigh</au><au>Gao, Long</au><au>Lan, Yemin</au><au>Manduchi, Elisabetta</au><au>Waite, Eric L</au><au>Wang, Amber W</au><au>Wells, Andrew</au><au>Kaestner, Klaus H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Collapse of the hepatic gene regulatory network in the absence of FoxA factors</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>2020-08-01</date><risdate>2020</risdate><volume>34</volume><issue>15-16</issue><spage>1039</spage><epage>1050</epage><pages>1039-1050</pages><issn>0890-9369</issn><eissn>1549-5477</eissn><abstract>The FoxA transcription factors are critical for liver development through their pioneering activity, which initiates a highly complex regulatory network thought to become progressively resistant to the loss of any individual hepatic transcription factor via mutual redundancy. To investigate the dispensability of FoxA factors for maintaining this regulatory network, we ablated all FoxA genes in the adult mouse liver. Remarkably, loss of FoxA caused rapid and massive reduction in the expression of critical liver genes. Activity of these genes was reduced back to the low levels of the fetal prehepatic endoderm stage, leading to necrosis and lethality within days. Mechanistically, we found FoxA proteins to be required for maintaining enhancer activity, chromatin accessibility, nucleosome positioning, and binding of HNF4α. Thus, the FoxA factors act continuously, guarding hepatic enhancer activity throughout adult life.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>32561546</pmid><doi>10.1101/gad.337691.120</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-1228-021X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0890-9369 |
| ispartof | Genes & development, 2020-08, Vol.34 (15-16), p.1039-1050 |
| issn | 0890-9369 1549-5477 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7397852 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Binding Sites Chromatin - metabolism Enhancer Elements, Genetic Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism Forkhead Transcription Factors - physiology Gene Expression Regulation Gene Knockdown Techniques Gene Regulatory Networks Hepatocyte Nuclear Factor 3-alpha - genetics Hepatocyte Nuclear Factor 3-beta - genetics Hepatocyte Nuclear Factor 3-gamma - genetics Hepatocyte Nuclear Factor 4 - metabolism Liver - metabolism Liver - pathology Liver Failure - etiology Liver Failure - pathology Male Mice Nucleosomes Research Paper |
| title | Collapse of the hepatic gene regulatory network in the absence of FoxA factors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T06%3A47%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Collapse%20of%20the%20hepatic%20gene%20regulatory%20network%20in%20the%20absence%20of%20FoxA%20factors&rft.jtitle=Genes%20&%20development&rft.au=Reizel,%20Yitzhak&rft.date=2020-08-01&rft.volume=34&rft.issue=15-16&rft.spage=1039&rft.epage=1050&rft.pages=1039-1050&rft.issn=0890-9369&rft.eissn=1549-5477&rft_id=info:doi/10.1101/gad.337691.120&rft_dat=%3Cpubmed_cross%3E32561546%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/32561546&rfr_iscdi=true |