Positive regulation of connexin32 transcription by hepatocyte nuclear factor-1alpha
Connexin32 (Cx32) encodes the predominant gap junction protein expressed by hepatocytes. We investigated the transcriptional control of Cx32 in expressing and nonexpressing rat liver cell lines and hypothesized that a putative hepatocyte nuclear factor-1 (HNF-1) binding site (centered at mp -187) in...
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| Veröffentlicht in: | Archives of biochemistry and biophysics 2002-11, Vol.407 (2), p.160 |
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| creator | Koffler, Lucas D Fernstrom, Martha J Akiyama, Taro E Gonzalez, Frank J Ruch, Randall J |
| description | Connexin32 (Cx32) encodes the predominant gap junction protein expressed by hepatocytes. We investigated the transcriptional control of Cx32 in expressing and nonexpressing rat liver cell lines and hypothesized that a putative hepatocyte nuclear factor-1 (HNF-1) binding site (centered at mp -187) in the liver-active, P1 promoter is essential for transcription of Cx32. HNF-1alpha was expressed by Cx32-expressing rat liver cell lines and bound the promoter at the -187 site, but was not expressed by non-Cx32-expressing hepatic lines. Stable transfection of non-Cx32-expressing WB-F344 rat liver epithelial cells with HNF-1alpha stimulated a transfected Cx32 promoter element (mp -244 to -33), binding of HNF-1alpha to the -187 site, and expression of endogenous Cx32. Site-directed mutagenesis of this HNF-1 binding site abolished HNF-1alpha binding and proximal promoter activity. Hepatic Cx32 expression was also significantly decreased in HNF-1alpha(-/-) mice. These data indicate that HNF-1alpha is a positive regulator of Cx32 expression in hepatic cells. |
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We investigated the transcriptional control of Cx32 in expressing and nonexpressing rat liver cell lines and hypothesized that a putative hepatocyte nuclear factor-1 (HNF-1) binding site (centered at mp -187) in the liver-active, P1 promoter is essential for transcription of Cx32. HNF-1alpha was expressed by Cx32-expressing rat liver cell lines and bound the promoter at the -187 site, but was not expressed by non-Cx32-expressing hepatic lines. Stable transfection of non-Cx32-expressing WB-F344 rat liver epithelial cells with HNF-1alpha stimulated a transfected Cx32 promoter element (mp -244 to -33), binding of HNF-1alpha to the -187 site, and expression of endogenous Cx32. Site-directed mutagenesis of this HNF-1 binding site abolished HNF-1alpha binding and proximal promoter activity. Hepatic Cx32 expression was also significantly decreased in HNF-1alpha(-/-) mice. These data indicate that HNF-1alpha is a positive regulator of Cx32 expression in hepatic cells.</description><identifier>ISSN: 0003-9861</identifier><identifier>PMID: 12413486</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Base Sequence ; Binding Sites ; Cell Line ; Connexins - biosynthesis ; Connexins - genetics ; DNA-Binding Proteins ; Gap Junction beta-1 Protein ; Hepatocyte Nuclear Factor 1 ; Hepatocyte Nuclear Factor 1-alpha ; Hepatocyte Nuclear Factor 1-beta ; Liver - metabolism ; Mice ; Mice, Knockout ; Nuclear Proteins ; Promoter Regions, Genetic ; Rats ; Rats, Inbred F344 ; Response Elements ; RNA, Messenger - biosynthesis ; Transcription Factors - genetics ; Transcription Factors - physiology ; Transcriptional Activation ; Transfection</subject><ispartof>Archives of biochemistry and biophysics, 2002-11, Vol.407 (2), p.160</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12413486$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koffler, Lucas D</creatorcontrib><creatorcontrib>Fernstrom, Martha J</creatorcontrib><creatorcontrib>Akiyama, Taro E</creatorcontrib><creatorcontrib>Gonzalez, Frank J</creatorcontrib><creatorcontrib>Ruch, Randall J</creatorcontrib><title>Positive regulation of connexin32 transcription by hepatocyte nuclear factor-1alpha</title><title>Archives of biochemistry and biophysics</title><addtitle>Arch Biochem Biophys</addtitle><description>Connexin32 (Cx32) encodes the predominant gap junction protein expressed by hepatocytes. We investigated the transcriptional control of Cx32 in expressing and nonexpressing rat liver cell lines and hypothesized that a putative hepatocyte nuclear factor-1 (HNF-1) binding site (centered at mp -187) in the liver-active, P1 promoter is essential for transcription of Cx32. HNF-1alpha was expressed by Cx32-expressing rat liver cell lines and bound the promoter at the -187 site, but was not expressed by non-Cx32-expressing hepatic lines. Stable transfection of non-Cx32-expressing WB-F344 rat liver epithelial cells with HNF-1alpha stimulated a transfected Cx32 promoter element (mp -244 to -33), binding of HNF-1alpha to the -187 site, and expression of endogenous Cx32. Site-directed mutagenesis of this HNF-1 binding site abolished HNF-1alpha binding and proximal promoter activity. Hepatic Cx32 expression was also significantly decreased in HNF-1alpha(-/-) mice. These data indicate that HNF-1alpha is a positive regulator of Cx32 expression in hepatic cells.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Binding Sites</subject><subject>Cell Line</subject><subject>Connexins - biosynthesis</subject><subject>Connexins - genetics</subject><subject>DNA-Binding Proteins</subject><subject>Gap Junction beta-1 Protein</subject><subject>Hepatocyte Nuclear Factor 1</subject><subject>Hepatocyte Nuclear Factor 1-alpha</subject><subject>Hepatocyte Nuclear Factor 1-beta</subject><subject>Liver - metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Nuclear Proteins</subject><subject>Promoter Regions, Genetic</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Response Elements</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - physiology</subject><subject>Transcriptional Activation</subject><subject>Transfection</subject><issn>0003-9861</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1j81KAzEURrNQ2lp9BckLDOQmaSZdSvEPCgp2X-6kd9rINAlJRpy3V_xZfYvDOfBdsIUQQjVra2DOrkp5FwJAGzljc5AalLZmwd5eY_HVfxDPdBwHrD4GHnvuYgj06YOSvGYMxWWfflg38RMlrNFNlXgY3UCYeY-uxtwADumE1-yyx6HQzd8u2e7hfrd5arYvj8-bu22TVto01jijlVz3wgFahSAkKEIFraLeSXVopSDdrawlMCg6K7WUzrRgO4T2W12y299sGrszHfYp-zPmaf9_Tn0BgktKRA</recordid><startdate>20021115</startdate><enddate>20021115</enddate><creator>Koffler, Lucas D</creator><creator>Fernstrom, Martha J</creator><creator>Akiyama, Taro E</creator><creator>Gonzalez, Frank J</creator><creator>Ruch, Randall J</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20021115</creationdate><title>Positive regulation of connexin32 transcription by hepatocyte nuclear factor-1alpha</title><author>Koffler, Lucas D ; Fernstrom, Martha J ; Akiyama, Taro E ; Gonzalez, Frank J ; Ruch, Randall J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p546-86c64329f0c1a83a10213ea3173efc23d720e4b588e16a0b82422c6718ba17643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Binding Sites</topic><topic>Cell Line</topic><topic>Connexins - biosynthesis</topic><topic>Connexins - genetics</topic><topic>DNA-Binding Proteins</topic><topic>Gap Junction beta-1 Protein</topic><topic>Hepatocyte Nuclear Factor 1</topic><topic>Hepatocyte Nuclear Factor 1-alpha</topic><topic>Hepatocyte Nuclear Factor 1-beta</topic><topic>Liver - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Nuclear Proteins</topic><topic>Promoter Regions, Genetic</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Response Elements</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - physiology</topic><topic>Transcriptional Activation</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koffler, Lucas D</creatorcontrib><creatorcontrib>Fernstrom, Martha J</creatorcontrib><creatorcontrib>Akiyama, Taro E</creatorcontrib><creatorcontrib>Gonzalez, Frank J</creatorcontrib><creatorcontrib>Ruch, Randall J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Archives of biochemistry and biophysics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koffler, Lucas D</au><au>Fernstrom, Martha J</au><au>Akiyama, Taro E</au><au>Gonzalez, Frank J</au><au>Ruch, Randall J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Positive regulation of connexin32 transcription by hepatocyte nuclear factor-1alpha</atitle><jtitle>Archives of biochemistry and biophysics</jtitle><addtitle>Arch Biochem Biophys</addtitle><date>2002-11-15</date><risdate>2002</risdate><volume>407</volume><issue>2</issue><spage>160</spage><pages>160-</pages><issn>0003-9861</issn><abstract>Connexin32 (Cx32) encodes the predominant gap junction protein expressed by hepatocytes. We investigated the transcriptional control of Cx32 in expressing and nonexpressing rat liver cell lines and hypothesized that a putative hepatocyte nuclear factor-1 (HNF-1) binding site (centered at mp -187) in the liver-active, P1 promoter is essential for transcription of Cx32. HNF-1alpha was expressed by Cx32-expressing rat liver cell lines and bound the promoter at the -187 site, but was not expressed by non-Cx32-expressing hepatic lines. Stable transfection of non-Cx32-expressing WB-F344 rat liver epithelial cells with HNF-1alpha stimulated a transfected Cx32 promoter element (mp -244 to -33), binding of HNF-1alpha to the -187 site, and expression of endogenous Cx32. Site-directed mutagenesis of this HNF-1 binding site abolished HNF-1alpha binding and proximal promoter activity. Hepatic Cx32 expression was also significantly decreased in HNF-1alpha(-/-) mice. These data indicate that HNF-1alpha is a positive regulator of Cx32 expression in hepatic cells.</abstract><cop>United States</cop><pmid>12413486</pmid></addata></record> |
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| ispartof | Archives of biochemistry and biophysics, 2002-11, Vol.407 (2), p.160 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Base Sequence Binding Sites Cell Line Connexins - biosynthesis Connexins - genetics DNA-Binding Proteins Gap Junction beta-1 Protein Hepatocyte Nuclear Factor 1 Hepatocyte Nuclear Factor 1-alpha Hepatocyte Nuclear Factor 1-beta Liver - metabolism Mice Mice, Knockout Nuclear Proteins Promoter Regions, Genetic Rats Rats, Inbred F344 Response Elements RNA, Messenger - biosynthesis Transcription Factors - genetics Transcription Factors - physiology Transcriptional Activation Transfection |
| title | Positive regulation of connexin32 transcription by hepatocyte nuclear factor-1alpha |
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