Identification of CTCF as a master regulator of the clustered protocadherin genes
The brain is a large and complex network of neurons. Specific neuronal connectivity is thought to be based on the combinatorial expression of the 52 protocadherins (Pcdh) membrane adhesion proteins, whereby each neuron expresses only a specific subset. Pcdh genes are arranged in tandem, in a cluster...
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| Veröffentlicht in: | Nucleic acids research 2012-04, Vol.40 (8), p.3378-3391 |
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| creator | Golan-Mashiach, Michal Grunspan, Moshe Emmanuel, Rafi Gibbs-Bar, Liron Dikstein, Rivka Shapiro, Ehud |
| description | The brain is a large and complex network of neurons. Specific neuronal connectivity is thought to be based on the combinatorial expression of the 52 protocadherins (Pcdh) membrane adhesion proteins, whereby each neuron expresses only a specific subset. Pcdh genes are arranged in tandem, in a cluster of three families: Pcdhα, Pcdhβ and Pcdhγ. The expression of each Pcdh gene is regulated by a promoter that has a regulatory conserved sequence element (CSE), common to all 52 genes. The mechanism and factors controlling individual Pcdh gene expression are currently unknown. Here we show that the promoter of each Pcdh gene contains a gene-specific conserved control region, termed specific sequence element (SSE), located adjacent and upstream to the CSE and activates transcription together with the CSE. We purified the complex that specifically binds the SSE-CSE region and identified the CCTC binding-factor (CTCF) as a key molecule that binds and activates Pcdh promoters. Our findings point to CTCF as a factor essential for Pcdh expression and probably governing neuronal connectivity. |
| doi_str_mv | 10.1093/nar/gkr1260 |
| format | Article |
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Specific neuronal connectivity is thought to be based on the combinatorial expression of the 52 protocadherins (Pcdh) membrane adhesion proteins, whereby each neuron expresses only a specific subset. Pcdh genes are arranged in tandem, in a cluster of three families: Pcdhα, Pcdhβ and Pcdhγ. The expression of each Pcdh gene is regulated by a promoter that has a regulatory conserved sequence element (CSE), common to all 52 genes. The mechanism and factors controlling individual Pcdh gene expression are currently unknown. Here we show that the promoter of each Pcdh gene contains a gene-specific conserved control region, termed specific sequence element (SSE), located adjacent and upstream to the CSE and activates transcription together with the CSE. We purified the complex that specifically binds the SSE-CSE region and identified the CCTC binding-factor (CTCF) as a key molecule that binds and activates Pcdh promoters. 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Specific neuronal connectivity is thought to be based on the combinatorial expression of the 52 protocadherins (Pcdh) membrane adhesion proteins, whereby each neuron expresses only a specific subset. Pcdh genes are arranged in tandem, in a cluster of three families: Pcdhα, Pcdhβ and Pcdhγ. The expression of each Pcdh gene is regulated by a promoter that has a regulatory conserved sequence element (CSE), common to all 52 genes. The mechanism and factors controlling individual Pcdh gene expression are currently unknown. Here we show that the promoter of each Pcdh gene contains a gene-specific conserved control region, termed specific sequence element (SSE), located adjacent and upstream to the CSE and activates transcription together with the CSE. We purified the complex that specifically binds the SSE-CSE region and identified the CCTC binding-factor (CTCF) as a key molecule that binds and activates Pcdh promoters. Our findings point to CTCF as a factor essential for Pcdh expression and probably governing neuronal connectivity.</description><subject>Base Sequence</subject><subject>Brain</subject><subject>Cadherins - biosynthesis</subject><subject>Cadherins - genetics</subject><subject>CCCTC-Binding Factor</subject><subject>Cell Line</subject><subject>Conserved Sequence</subject><subject>Gene Regulation, Chromatin and Epigenetics</subject><subject>Humans</subject><subject>Mass Spectrometry</subject><subject>Molecular Sequence Data</subject><subject>Multigene Family</subject><subject>Neural networks</subject><subject>Neurons</subject><subject>Promoter Regions, Genetic</subject><subject>Promoters</subject><subject>protocadherin</subject><subject>Repressor Proteins - metabolism</subject><subject>Repressor Proteins - physiology</subject><subject>Transcription</subject><subject>Transcription, Genetic</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUc9LwzAYDaK4OT15lxwFqfvyo11yEWQ4HQxEmOeQJulW7ZqZtIL_vS2bQ29-l-_wHo_3A6FLArcEJBvXOoxX74HQDI7QkLCMJlxm9BgNgUGaEOBigM5ifAMgnKT8FA0opQSEkEP0MreubsqiNLopfY19gafL6QzriDXe6Ni4gINbtZVufOjRZu2wqdoecBZvg2-80XbtQlnjlatdPEcnha6iu9j_EXqdPSynT8ni-XE-vV8khgtoEk11mkGeUpg4xguRZtxOLBOZsVQb4FyKHCS3gpCMG6mtNFbaPC1oPulyETZCdzvdbZtvnDVdjKArtQ3lRocv5XWp_iJ1uVYr_6lYdyJjncD1XiD4j9bFRm3KaFxV6dr5NirS19UZAfoPKsi061_2qjc7qgk-xuCKgyMCqt9LdXup_V4d--p3iAP3ZyD2Dd8Qkgw</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Golan-Mashiach, Michal</creator><creator>Grunspan, Moshe</creator><creator>Emmanuel, Rafi</creator><creator>Gibbs-Bar, Liron</creator><creator>Dikstein, Rivka</creator><creator>Shapiro, Ehud</creator><general>Oxford University 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>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20120401</creationdate><title>Identification of CTCF as a master regulator of the clustered protocadherin genes</title><author>Golan-Mashiach, Michal ; Grunspan, Moshe ; Emmanuel, Rafi ; Gibbs-Bar, Liron ; Dikstein, Rivka ; Shapiro, Ehud</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-a2a560b5207e34f8564d7d386cd2ac04498b094d81164c9ad9cd9db5f2b703013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Base Sequence</topic><topic>Brain</topic><topic>Cadherins - biosynthesis</topic><topic>Cadherins - genetics</topic><topic>CCCTC-Binding Factor</topic><topic>Cell Line</topic><topic>Conserved Sequence</topic><topic>Gene Regulation, Chromatin and Epigenetics</topic><topic>Humans</topic><topic>Mass Spectrometry</topic><topic>Molecular Sequence Data</topic><topic>Multigene Family</topic><topic>Neural networks</topic><topic>Neurons</topic><topic>Promoter Regions, Genetic</topic><topic>Promoters</topic><topic>protocadherin</topic><topic>Repressor Proteins - metabolism</topic><topic>Repressor Proteins - physiology</topic><topic>Transcription</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Golan-Mashiach, Michal</creatorcontrib><creatorcontrib>Grunspan, Moshe</creatorcontrib><creatorcontrib>Emmanuel, Rafi</creatorcontrib><creatorcontrib>Gibbs-Bar, Liron</creatorcontrib><creatorcontrib>Dikstein, Rivka</creatorcontrib><creatorcontrib>Shapiro, Ehud</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>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Golan-Mashiach, Michal</au><au>Grunspan, Moshe</au><au>Emmanuel, Rafi</au><au>Gibbs-Bar, Liron</au><au>Dikstein, Rivka</au><au>Shapiro, Ehud</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of CTCF as a master regulator of the clustered protocadherin genes</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>40</volume><issue>8</issue><spage>3378</spage><epage>3391</epage><pages>3378-3391</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>The brain is a large and complex network of neurons. Specific neuronal connectivity is thought to be based on the combinatorial expression of the 52 protocadherins (Pcdh) membrane adhesion proteins, whereby each neuron expresses only a specific subset. Pcdh genes are arranged in tandem, in a cluster of three families: Pcdhα, Pcdhβ and Pcdhγ. The expression of each Pcdh gene is regulated by a promoter that has a regulatory conserved sequence element (CSE), common to all 52 genes. The mechanism and factors controlling individual Pcdh gene expression are currently unknown. Here we show that the promoter of each Pcdh gene contains a gene-specific conserved control region, termed specific sequence element (SSE), located adjacent and upstream to the CSE and activates transcription together with the CSE. We purified the complex that specifically binds the SSE-CSE region and identified the CCTC binding-factor (CTCF) as a key molecule that binds and activates Pcdh promoters. 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| subjects | Base Sequence Brain Cadherins - biosynthesis Cadherins - genetics CCCTC-Binding Factor Cell Line Conserved Sequence Gene Regulation, Chromatin and Epigenetics Humans Mass Spectrometry Molecular Sequence Data Multigene Family Neural networks Neurons Promoter Regions, Genetic Promoters protocadherin Repressor Proteins - metabolism Repressor Proteins - physiology Transcription Transcription, Genetic |
| title | Identification of CTCF as a master regulator of the clustered protocadherin genes |
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