BCL6 positively regulates AID and germinal center gene expression via repression of miR-155
The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose de-regulation is involved in lymphomagenesis. Although substantial evidence indicates that BCL6 exerts its function by repressing the transcription of hundreds of protein-coding...
Gespeichert in:
| Veröffentlicht in: | The Journal of experimental medicine 2012-12, Vol.209 (13), p.2455-2465 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2465 |
|---|---|
| container_issue | 13 |
| container_start_page | 2455 |
| container_title | The Journal of experimental medicine |
| container_volume | 209 |
| creator | Basso, Katia Schneider, Christof Shen, Qiong Holmes, Antony B Setty, Manu Leslie, Christina Dalla-Favera, Riccardo |
| description | The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose de-regulation is involved in lymphomagenesis. Although substantial evidence indicates that BCL6 exerts its function by repressing the transcription of hundreds of protein-coding genes, its potential role in regulating gene expression via microRNAs (miRNAs) is not known. We have identified a core of 15 miRNAs that show binding of BCL6 in their genomic loci and are down-regulated in GC B cells. Among BCL6 validated targets, miR-155 and miR-361 directly modulate AID expression, indicating that via repression of these miRNAs, BCL6 up-regulates AID. Similarly, the expression of additional genes relevant for the GC phenotype, including SPI1, IRF8, and MYB, appears to be sustained via BCL6-mediated repression of miR-155. These findings identify a novel mechanism by which BCL6, in addition to repressing protein coding genes, promotes the expression of important GC functions by repressing specific miRNAs. |
| doi_str_mv | 10.1084/jem.20121387 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3526356</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1551641220</sourcerecordid><originalsourceid>FETCH-LOGICAL-c483t-8fd9ca050af3386f7ff927557dfe879443423dfc59e7453f06c2d7bff9e03e633</originalsourceid><addsrcrecordid>eNqFkUlLBDEQhYMoOi43z5KjB1sre_dF0HGFAUH05CHE7soY6WVMegb99_agDnryVBT11aNePUL2GRwzyOXJKzbHHBhnIjdrZMSUhKxQIl8nIwDOMwZgtsh2Sq8ATEqlN8kWF0xrofSIPJ2PJ5rOuhT6sMD6g0aczmvXY6JntxfUtRWdYmxC62paYttjHPoWKb7PIqYUupYughu2Vm3naRPuM6bULtnwrk649113yOPV5cP4JpvcXd-OzyZZKXPRZ7mvitKBAueFyLU33hfcKGUqj7kppBSSi8qXqkAjlfCgS16Z54FCEKiF2CGnX7qz-XOD1fLM6Go7i6Fx8cN2Lti_kza82Gm3sELx5RcGgcNvgdi9zTH1tgmpxLp2LXbzZAcvTEvGOfyPciO4AZ6zAT36QsvYpRTRry5iYJfR2SE6-xPdgB_8drGCf7ISn3zSlIA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1273270281</pqid></control><display><type>article</type><title>BCL6 positively regulates AID and germinal center gene expression via repression of miR-155</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Basso, Katia ; Schneider, Christof ; Shen, Qiong ; Holmes, Antony B ; Setty, Manu ; Leslie, Christina ; Dalla-Favera, Riccardo</creator><creatorcontrib>Basso, Katia ; Schneider, Christof ; Shen, Qiong ; Holmes, Antony B ; Setty, Manu ; Leslie, Christina ; Dalla-Favera, Riccardo</creatorcontrib><description>The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose de-regulation is involved in lymphomagenesis. Although substantial evidence indicates that BCL6 exerts its function by repressing the transcription of hundreds of protein-coding genes, its potential role in regulating gene expression via microRNAs (miRNAs) is not known. We have identified a core of 15 miRNAs that show binding of BCL6 in their genomic loci and are down-regulated in GC B cells. Among BCL6 validated targets, miR-155 and miR-361 directly modulate AID expression, indicating that via repression of these miRNAs, BCL6 up-regulates AID. Similarly, the expression of additional genes relevant for the GC phenotype, including SPI1, IRF8, and MYB, appears to be sustained via BCL6-mediated repression of miR-155. These findings identify a novel mechanism by which BCL6, in addition to repressing protein coding genes, promotes the expression of important GC functions by repressing specific miRNAs.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20121387</identifier><identifier>PMID: 23166356</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>3' Untranslated Regions ; Animals ; B-Lymphocytes - metabolism ; Base Sequence ; Binding Sites - genetics ; Cell Line ; Cytidine Deaminase - genetics ; Cytidine Deaminase - metabolism ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Gene Expression Regulation ; Germinal Center - cytology ; Germinal Center - metabolism ; HEK293 Cells ; Humans ; Mice ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Proto-Oncogene Proteins c-bcl-6</subject><ispartof>The Journal of experimental medicine, 2012-12, Vol.209 (13), p.2455-2465</ispartof><rights>2012 Basso et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-8fd9ca050af3386f7ff927557dfe879443423dfc59e7453f06c2d7bff9e03e633</citedby><cites>FETCH-LOGICAL-c483t-8fd9ca050af3386f7ff927557dfe879443423dfc59e7453f06c2d7bff9e03e633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23166356$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Basso, Katia</creatorcontrib><creatorcontrib>Schneider, Christof</creatorcontrib><creatorcontrib>Shen, Qiong</creatorcontrib><creatorcontrib>Holmes, Antony B</creatorcontrib><creatorcontrib>Setty, Manu</creatorcontrib><creatorcontrib>Leslie, Christina</creatorcontrib><creatorcontrib>Dalla-Favera, Riccardo</creatorcontrib><title>BCL6 positively regulates AID and germinal center gene expression via repression of miR-155</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose de-regulation is involved in lymphomagenesis. Although substantial evidence indicates that BCL6 exerts its function by repressing the transcription of hundreds of protein-coding genes, its potential role in regulating gene expression via microRNAs (miRNAs) is not known. We have identified a core of 15 miRNAs that show binding of BCL6 in their genomic loci and are down-regulated in GC B cells. Among BCL6 validated targets, miR-155 and miR-361 directly modulate AID expression, indicating that via repression of these miRNAs, BCL6 up-regulates AID. Similarly, the expression of additional genes relevant for the GC phenotype, including SPI1, IRF8, and MYB, appears to be sustained via BCL6-mediated repression of miR-155. These findings identify a novel mechanism by which BCL6, in addition to repressing protein coding genes, promotes the expression of important GC functions by repressing specific miRNAs.</description><subject>3' Untranslated Regions</subject><subject>Animals</subject><subject>B-Lymphocytes - metabolism</subject><subject>Base Sequence</subject><subject>Binding Sites - genetics</subject><subject>Cell Line</subject><subject>Cytidine Deaminase - genetics</subject><subject>Cytidine Deaminase - metabolism</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Germinal Center - cytology</subject><subject>Germinal Center - metabolism</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Mice</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Proto-Oncogene Proteins c-bcl-6</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUlLBDEQhYMoOi43z5KjB1sre_dF0HGFAUH05CHE7soY6WVMegb99_agDnryVBT11aNePUL2GRwzyOXJKzbHHBhnIjdrZMSUhKxQIl8nIwDOMwZgtsh2Sq8ATEqlN8kWF0xrofSIPJ2PJ5rOuhT6sMD6g0aczmvXY6JntxfUtRWdYmxC62paYttjHPoWKb7PIqYUupYughu2Vm3naRPuM6bULtnwrk649113yOPV5cP4JpvcXd-OzyZZKXPRZ7mvitKBAueFyLU33hfcKGUqj7kppBSSi8qXqkAjlfCgS16Z54FCEKiF2CGnX7qz-XOD1fLM6Go7i6Fx8cN2Lti_kza82Gm3sELx5RcGgcNvgdi9zTH1tgmpxLp2LXbzZAcvTEvGOfyPciO4AZ6zAT36QsvYpRTRry5iYJfR2SE6-xPdgB_8drGCf7ISn3zSlIA</recordid><startdate>20121217</startdate><enddate>20121217</enddate><creator>Basso, Katia</creator><creator>Schneider, Christof</creator><creator>Shen, Qiong</creator><creator>Holmes, Antony B</creator><creator>Setty, Manu</creator><creator>Leslie, Christina</creator><creator>Dalla-Favera, Riccardo</creator><general>The Rockefeller 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>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20121217</creationdate><title>BCL6 positively regulates AID and germinal center gene expression via repression of miR-155</title><author>Basso, Katia ; Schneider, Christof ; Shen, Qiong ; Holmes, Antony B ; Setty, Manu ; Leslie, Christina ; Dalla-Favera, Riccardo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-8fd9ca050af3386f7ff927557dfe879443423dfc59e7453f06c2d7bff9e03e633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>3' Untranslated Regions</topic><topic>Animals</topic><topic>B-Lymphocytes - metabolism</topic><topic>Base Sequence</topic><topic>Binding Sites - genetics</topic><topic>Cell Line</topic><topic>Cytidine Deaminase - genetics</topic><topic>Cytidine Deaminase - metabolism</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Germinal Center - cytology</topic><topic>Germinal Center - metabolism</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Mice</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Proto-Oncogene Proteins c-bcl-6</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Basso, Katia</creatorcontrib><creatorcontrib>Schneider, Christof</creatorcontrib><creatorcontrib>Shen, Qiong</creatorcontrib><creatorcontrib>Holmes, Antony B</creatorcontrib><creatorcontrib>Setty, Manu</creatorcontrib><creatorcontrib>Leslie, Christina</creatorcontrib><creatorcontrib>Dalla-Favera, Riccardo</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>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Basso, Katia</au><au>Schneider, Christof</au><au>Shen, Qiong</au><au>Holmes, Antony B</au><au>Setty, Manu</au><au>Leslie, Christina</au><au>Dalla-Favera, Riccardo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BCL6 positively regulates AID and germinal center gene expression via repression of miR-155</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2012-12-17</date><risdate>2012</risdate><volume>209</volume><issue>13</issue><spage>2455</spage><epage>2465</epage><pages>2455-2465</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose de-regulation is involved in lymphomagenesis. Although substantial evidence indicates that BCL6 exerts its function by repressing the transcription of hundreds of protein-coding genes, its potential role in regulating gene expression via microRNAs (miRNAs) is not known. We have identified a core of 15 miRNAs that show binding of BCL6 in their genomic loci and are down-regulated in GC B cells. Among BCL6 validated targets, miR-155 and miR-361 directly modulate AID expression, indicating that via repression of these miRNAs, BCL6 up-regulates AID. Similarly, the expression of additional genes relevant for the GC phenotype, including SPI1, IRF8, and MYB, appears to be sustained via BCL6-mediated repression of miR-155. These findings identify a novel mechanism by which BCL6, in addition to repressing protein coding genes, promotes the expression of important GC functions by repressing specific miRNAs.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>23166356</pmid><doi>10.1084/jem.20121387</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1007 |
| ispartof | The Journal of experimental medicine, 2012-12, Vol.209 (13), p.2455-2465 |
| issn | 0022-1007 1540-9538 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3526356 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | 3' Untranslated Regions Animals B-Lymphocytes - metabolism Base Sequence Binding Sites - genetics Cell Line Cytidine Deaminase - genetics Cytidine Deaminase - metabolism DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Gene Expression Regulation Germinal Center - cytology Germinal Center - metabolism HEK293 Cells Humans Mice MicroRNAs - genetics MicroRNAs - metabolism Proto-Oncogene Proteins c-bcl-6 |
| title | BCL6 positively regulates AID and germinal center gene expression via repression of miR-155 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T15%3A19%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=BCL6%20positively%20regulates%20AID%20and%20germinal%20center%20gene%20expression%20via%20repression%20of%20miR-155&rft.jtitle=The%20Journal%20of%20experimental%20medicine&rft.au=Basso,%20Katia&rft.date=2012-12-17&rft.volume=209&rft.issue=13&rft.spage=2455&rft.epage=2465&rft.pages=2455-2465&rft.issn=0022-1007&rft.eissn=1540-9538&rft_id=info:doi/10.1084/jem.20121387&rft_dat=%3Cproquest_pubme%3E1551641220%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1273270281&rft_id=info:pmid/23166356&rfr_iscdi=true |