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The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats
Maintenance of specific heterochromatic domains is crucial for genome stability. In eukaryotic cells, a fraction of the tandem‐repeated ribosomal RNA (rRNA) genes is organized in the heterochromatic structures. The principal determinant of rDNA silencing is the nucleolar remodelling complex, NoRC, t...
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Published in: | The EMBO journal 2010-07, Vol.29 (13), p.2135-2146 |
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description | Maintenance of specific heterochromatic domains is crucial for genome stability. In eukaryotic cells, a fraction of the tandem‐repeated ribosomal RNA (rRNA) genes is organized in the heterochromatic structures. The principal determinant of rDNA silencing is the nucleolar remodelling complex, NoRC, that consists of TIP5 (TTF‐1‐interacting protein‐5) and the ATPase SNF2h. Here we showed that TIP5 not only mediates the establishment of rDNA silencing but also the formation of perinucleolar heterochromatin that contains centric and pericentric repeats. Our data indicated that the TIP5‐mediated heterochromatin is indispensable for stability of silent rRNA genes and of major and minor satellite repeats. Moreover, depletion of TIP5 impairs rDNA silencing, upregulates rDNA transcription levels and induces cell transformation. These findings point to a role of TIP5 in protecting genome stability and suggest that it can play a role in the cellular transformation process. |
doi_str_mv | 10.1038/emboj.2010.17 |
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In eukaryotic cells, a fraction of the tandem‐repeated ribosomal RNA (rRNA) genes is organized in the heterochromatic structures. The principal determinant of rDNA silencing is the nucleolar remodelling complex, NoRC, that consists of TIP5 (TTF‐1‐interacting protein‐5) and the ATPase SNF2h. Here we showed that TIP5 not only mediates the establishment of rDNA silencing but also the formation of perinucleolar heterochromatin that contains centric and pericentric repeats. Our data indicated that the TIP5‐mediated heterochromatin is indispensable for stability of silent rRNA genes and of major and minor satellite repeats. Moreover, depletion of TIP5 impairs rDNA silencing, upregulates rDNA transcription levels and induces cell transformation. These findings point to a role of TIP5 in protecting genome stability and suggest that it can play a role in the cellular transformation process.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/emboj.2010.17</identifier><identifier>PMID: 20168299</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; Cell Proliferation ; Cellular Biology ; Chromosomal Proteins, Non-Histone - metabolism ; Deoxyribonucleic acid ; DNA ; DNA, Ribosomal - genetics ; EMBO09 ; EMBO13 ; Gene Silencing ; Genes, rRNA ; Genomic Instability ; genomic stability ; Genomics ; heterochromatin ; Heterochromatin - metabolism ; Life Sciences ; Mice ; Molecular biology ; NIH 3T3 Cells ; NoRC ; Proteins ; rDNA silencing ; Ribonucleic acid ; RNA</subject><ispartof>The EMBO journal, 2010-07, Vol.29 (13), p.2135-2146</ispartof><rights>European Molecular Biology Organization 2010</rights><rights>Copyright © 2010 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Jul 7, 2010</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2010, European Molecular Biology Organization 2010 European Molecular Biology Organization</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6947-8898af705d41e1d51cd6b37f76b6d01a3cb72b4768b4574d4457311965542bb53</citedby><cites>FETCH-LOGICAL-c6947-8898af705d41e1d51cd6b37f76b6d01a3cb72b4768b4574d4457311965542bb53</cites><orcidid>0000-0003-0961-8838</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/PMC2905252/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905252/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20168299$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00505354$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Guetg, Claudio</creatorcontrib><creatorcontrib>Lienemann, Philipp</creatorcontrib><creatorcontrib>Sirri, Valentina</creatorcontrib><creatorcontrib>Grummt, Ingrid</creatorcontrib><creatorcontrib>Hernandez-Verdun, Danièle</creatorcontrib><creatorcontrib>Hottiger, Michael O</creatorcontrib><creatorcontrib>Fussenegger, Martin</creatorcontrib><creatorcontrib>Santoro, Raffaella</creatorcontrib><title>The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Maintenance of specific heterochromatic domains is crucial for genome stability. In eukaryotic cells, a fraction of the tandem‐repeated ribosomal RNA (rRNA) genes is organized in the heterochromatic structures. The principal determinant of rDNA silencing is the nucleolar remodelling complex, NoRC, that consists of TIP5 (TTF‐1‐interacting protein‐5) and the ATPase SNF2h. Here we showed that TIP5 not only mediates the establishment of rDNA silencing but also the formation of perinucleolar heterochromatin that contains centric and pericentric repeats. Our data indicated that the TIP5‐mediated heterochromatin is indispensable for stability of silent rRNA genes and of major and minor satellite repeats. Moreover, depletion of TIP5 impairs rDNA silencing, upregulates rDNA transcription levels and induces cell transformation. These findings point to a role of TIP5 in protecting genome stability and suggest that it can play a role in the cellular transformation process.</description><subject>Animals</subject><subject>Cell Proliferation</subject><subject>Cellular Biology</subject><subject>Chromosomal Proteins, Non-Histone - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Ribosomal - genetics</subject><subject>EMBO09</subject><subject>EMBO13</subject><subject>Gene Silencing</subject><subject>Genes, rRNA</subject><subject>Genomic Instability</subject><subject>genomic stability</subject><subject>Genomics</subject><subject>heterochromatin</subject><subject>Heterochromatin - metabolism</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Molecular biology</subject><subject>NIH 3T3 Cells</subject><subject>NoRC</subject><subject>Proteins</subject><subject>rDNA silencing</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqFks1v0zAYxiMEYt3gyBUZLhOHFNvxR3JBKtXYQKWIqQhulpM4jUsSF9sd63-P05QAk4CLP3_P875-_UbREwSnCCbpS9XmZjPFsN_ze9EEEQZjDDm9H00gZigmKM1OolPnNhBCmnL0MDoJOEtxlk0iu6oVWJrrOShMu23ULWhVqaVXDvhwUyuvrClqa1rpdQcqY_uF6YDsSuC8zHWj_R6YCjjdqM4De72cgbXqgkGPFOEsiJXVBbBqq6R3j6IHlWycenycz6JPby5W86t48eHy7Xy2iAuWER6naZbKikNaEqRQSVFRsjzhFWc5KyGSSZFznBPO0pxQTkoSxgShjFFKcJ7T5Cx6Nfhud3l41CET2Yit1a20e2GkFn_edLoWa3MjcAYppjgYvBgM6juyq9lC9GehnpAmlNygwJ4fg1nzbaecF612hWoa2Smzc4JTknJIDq7_IZOEEYwYC-TzO-TG7GwXaiYYxDwJv8wDFA9QYY1zVlVjpgiKvkPEoUNE3yEC9fzT36sy0j9bIgB0AL6HD93_201cvH_9rl8fjKeDzgVJt1b2V7Z_y-TZIOik31k1RjpQo-nxddp5dTsi0n4VjCecis_LS0H54svHVToPpfsBa23xuA</recordid><startdate>20100707</startdate><enddate>20100707</enddate><creator>Guetg, Claudio</creator><creator>Lienemann, Philipp</creator><creator>Sirri, Valentina</creator><creator>Grummt, Ingrid</creator><creator>Hernandez-Verdun, Danièle</creator><creator>Hottiger, Michael O</creator><creator>Fussenegger, Martin</creator><creator>Santoro, Raffaella</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><general>EMBO Press</general><general>Nature Publishing Group</general><scope>BSCLL</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0961-8838</orcidid></search><sort><creationdate>20100707</creationdate><title>The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats</title><author>Guetg, Claudio ; Lienemann, Philipp ; Sirri, Valentina ; Grummt, Ingrid ; Hernandez-Verdun, Danièle ; Hottiger, Michael O ; Fussenegger, Martin ; Santoro, Raffaella</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6947-8898af705d41e1d51cd6b37f76b6d01a3cb72b4768b4574d4457311965542bb53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Cell Proliferation</topic><topic>Cellular Biology</topic><topic>Chromosomal Proteins, Non-Histone - 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subjects | Animals Cell Proliferation Cellular Biology Chromosomal Proteins, Non-Histone - metabolism Deoxyribonucleic acid DNA DNA, Ribosomal - genetics EMBO09 EMBO13 Gene Silencing Genes, rRNA Genomic Instability genomic stability Genomics heterochromatin Heterochromatin - metabolism Life Sciences Mice Molecular biology NIH 3T3 Cells NoRC Proteins rDNA silencing Ribonucleic acid RNA |
title | The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats |
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