Chromatin-Bound IκBα Regulates a Subset of Polycomb Target Genes in Differentiation and Cancer
IκB proteins are the primary inhibitors of NF-κB. Here, we demonstrate that sumoylated and phosphorylated IκBα accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chromatin-bound IκBα modulates Polycomb recruitment and imp...
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| Veröffentlicht in: | Cancer cell 2013-08, Vol.24 (2), p.151-166 |
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| creator | Mulero, María Carmen Ferres-Marco, Dolors Islam, Abul Margalef, Pol Pecoraro, Matteo Toll, Agustí Drechsel, Nils Charneco, Cristina Davis, Shelly Bellora, Nicolás Gallardo, Fernando López-Arribillaga, Erika Asensio-Juan, Elena Rodilla, Verónica González, Jessica Iglesias, Mar Shih, Vincent Mar Albà, M. Di Croce, Luciano Hoffmann, Alexander Miyamoto, Shigeki Villà-Freixa, Jordi López-Bigas, Nuria Keyes, William M. Domínguez, María Bigas, Anna Espinosa, Lluís |
| description | IκB proteins are the primary inhibitors of NF-κB. Here, we demonstrate that sumoylated and phosphorylated IκBα accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chromatin-bound IκBα modulates Polycomb recruitment and imparts their competence to be activated by TNFα. Mutations in the Drosophila IκBα gene cactus enhance the homeotic phenotype of Polycomb mutants, which is not counteracted by mutations in dorsal/NF-κB. Oncogenic transformation of keratinocytes results in cytoplasmic IκBα translocation associated with a massive activation of Hox. Accumulation of cytoplasmic IκBα was found in squamous cell carcinoma (SCC) associated with IKK activation and HOX upregulation.
[Display omitted]
•Sumoylated and phosphorylated IκBα binds H2A and H4 in keratinocytes•IκBα regulates keratinocyte differentiation and transformation•IκBα regulates Polycomb chromatin release and HOX expression in response to TNFα•IκBα cooperates with Polycomb in Drosophila patterning |
| doi_str_mv | 10.1016/j.ccr.2013.06.003 |
| format | Article |
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[Display omitted]
•Sumoylated and phosphorylated IκBα binds H2A and H4 in keratinocytes•IκBα regulates keratinocyte differentiation and transformation•IκBα regulates Polycomb chromatin release and HOX expression in response to TNFα•IκBα cooperates with Polycomb in Drosophila patterning</description><identifier>ISSN: 1535-6108</identifier><identifier>EISSN: 1878-3686</identifier><identifier>DOI: 10.1016/j.ccr.2013.06.003</identifier><identifier>PMID: 23850221</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Cell Differentiation - genetics ; Cell Nucleus - genetics ; Cell Nucleus - metabolism ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Cell Transformation, Neoplastic - pathology ; Chromatin - genetics ; Chromatin - metabolism ; Cèl·lules ; Drosophila ; HEK293 Cells ; Histones - genetics ; Histones - metabolism ; Humans ; I-kappa B Proteins - genetics ; I-kappa B Proteins - metabolism ; Keratinocytes - cytology ; Keratinocytes - metabolism ; Mice ; Mice, Inbred C57BL ; NF-KappaB Inhibitor alpha ; Pell ; Signal Transduction ; Skin Neoplasms - genetics ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; Tumors</subject><ispartof>Cancer cell, 2013-08, Vol.24 (2), p.151-166</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><rights>info:eu-repo/semantics/openAccess © Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.ccr.2013.06.003 that appeared in the journal Cancer Cell. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: <a href="http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-license">http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-license</a></rights><rights>2013 Elsevier Inc. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-defe695374ea69e14669ca62bdfad4976f3883f7ff8fbd943dbe685c36e7a13f3</citedby><cites>FETCH-LOGICAL-c526t-defe695374ea69e14669ca62bdfad4976f3883f7ff8fbd943dbe685c36e7a13f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1535610813002791$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,26951,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23850221$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mulero, María Carmen</creatorcontrib><creatorcontrib>Ferres-Marco, Dolors</creatorcontrib><creatorcontrib>Islam, Abul</creatorcontrib><creatorcontrib>Margalef, Pol</creatorcontrib><creatorcontrib>Pecoraro, Matteo</creatorcontrib><creatorcontrib>Toll, Agustí</creatorcontrib><creatorcontrib>Drechsel, Nils</creatorcontrib><creatorcontrib>Charneco, Cristina</creatorcontrib><creatorcontrib>Davis, Shelly</creatorcontrib><creatorcontrib>Bellora, Nicolás</creatorcontrib><creatorcontrib>Gallardo, Fernando</creatorcontrib><creatorcontrib>López-Arribillaga, Erika</creatorcontrib><creatorcontrib>Asensio-Juan, Elena</creatorcontrib><creatorcontrib>Rodilla, Verónica</creatorcontrib><creatorcontrib>González, Jessica</creatorcontrib><creatorcontrib>Iglesias, Mar</creatorcontrib><creatorcontrib>Shih, Vincent</creatorcontrib><creatorcontrib>Mar Albà, M.</creatorcontrib><creatorcontrib>Di Croce, Luciano</creatorcontrib><creatorcontrib>Hoffmann, Alexander</creatorcontrib><creatorcontrib>Miyamoto, Shigeki</creatorcontrib><creatorcontrib>Villà-Freixa, Jordi</creatorcontrib><creatorcontrib>López-Bigas, Nuria</creatorcontrib><creatorcontrib>Keyes, William M.</creatorcontrib><creatorcontrib>Domínguez, María</creatorcontrib><creatorcontrib>Bigas, Anna</creatorcontrib><creatorcontrib>Espinosa, Lluís</creatorcontrib><title>Chromatin-Bound IκBα Regulates a Subset of Polycomb Target Genes in Differentiation and Cancer</title><title>Cancer cell</title><addtitle>Cancer Cell</addtitle><description>IκB proteins are the primary inhibitors of NF-κB. Here, we demonstrate that sumoylated and phosphorylated IκBα accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chromatin-bound IκBα modulates Polycomb recruitment and imparts their competence to be activated by TNFα. Mutations in the Drosophila IκBα gene cactus enhance the homeotic phenotype of Polycomb mutants, which is not counteracted by mutations in dorsal/NF-κB. Oncogenic transformation of keratinocytes results in cytoplasmic IκBα translocation associated with a massive activation of Hox. Accumulation of cytoplasmic IκBα was found in squamous cell carcinoma (SCC) associated with IKK activation and HOX upregulation.
[Display omitted]
•Sumoylated and phosphorylated IκBα binds H2A and H4 in keratinocytes•IκBα regulates keratinocyte differentiation and transformation•IκBα regulates Polycomb chromatin release and HOX expression in response to TNFα•IκBα cooperates with Polycomb in Drosophila patterning</description><subject>Animals</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Nucleus - genetics</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Cell Transformation, Neoplastic - pathology</subject><subject>Chromatin - genetics</subject><subject>Chromatin - metabolism</subject><subject>Cèl·lules</subject><subject>Drosophila</subject><subject>HEK293 Cells</subject><subject>Histones - genetics</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>I-kappa B Proteins - genetics</subject><subject>I-kappa B Proteins - metabolism</subject><subject>Keratinocytes - cytology</subject><subject>Keratinocytes - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>NF-KappaB Inhibitor alpha</subject><subject>Pell</subject><subject>Signal Transduction</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>Tumors</subject><issn>1535-6108</issn><issn>1878-3686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>XX2</sourceid><recordid>eNp9kctu1DAUhi0Eohd4ADYoSzYJviTHiZCQ6AClUiUQlLVx7OOpR0lc7KRSH4ttH6LPhIcpo7JhYfl2_s-_z0_IC0YrRhm83lTGxIpTJioKFaXiETlkrWxLAS08zutGNCUw2h6Qo5Q2NGuY7J6SAy7ahnLODsmP1WUMo579VJ6EZbLF2d3tyd2v4iuul0HPmApdfFv6hHMRXPElDDcmjH1xoeM6H53ilCv8VLz3zmHEafYZFaZCZ9JKTwbjM_LE6SHh8_v5mHz_-OFi9ak8_3x6tnp3XpqGw1xadAhdI2SNGjpkNUBnNPDeOm3rToITbSucdK51ve1qYXuEtjECUGomnDgmb3fcq6Uf0ZrsJepBXUU_6nijgvbq35vJX6p1uFaiAw5SZgDbAUxajIqYvRs9_xHuN9vBqeRKsEZSnjWv7h-N4eeCaVajTwaHQU8YlqQYABUdq0XzAB9DShHd3hqjapum2qicptqmqSionGbWvHz4p73ib3y54M2uAHNnrz1GlYzH3Hbrs-dZ2eD_g_8NlUey1g</recordid><startdate>20130812</startdate><enddate>20130812</enddate><creator>Mulero, María Carmen</creator><creator>Ferres-Marco, Dolors</creator><creator>Islam, Abul</creator><creator>Margalef, Pol</creator><creator>Pecoraro, Matteo</creator><creator>Toll, Agustí</creator><creator>Drechsel, Nils</creator><creator>Charneco, Cristina</creator><creator>Davis, Shelly</creator><creator>Bellora, Nicolás</creator><creator>Gallardo, Fernando</creator><creator>López-Arribillaga, Erika</creator><creator>Asensio-Juan, Elena</creator><creator>Rodilla, Verónica</creator><creator>González, Jessica</creator><creator>Iglesias, Mar</creator><creator>Shih, Vincent</creator><creator>Mar Albà, M.</creator><creator>Di Croce, Luciano</creator><creator>Hoffmann, Alexander</creator><creator>Miyamoto, Shigeki</creator><creator>Villà-Freixa, Jordi</creator><creator>López-Bigas, Nuria</creator><creator>Keyes, William M.</creator><creator>Domínguez, María</creator><creator>Bigas, Anna</creator><creator>Espinosa, Lluís</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</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>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>XX2</scope><scope>5PM</scope></search><sort><creationdate>20130812</creationdate><title>Chromatin-Bound IκBα Regulates a Subset of Polycomb Target Genes in Differentiation and Cancer</title><author>Mulero, María Carmen ; Ferres-Marco, Dolors ; Islam, Abul ; Margalef, Pol ; Pecoraro, Matteo ; Toll, Agustí ; Drechsel, Nils ; Charneco, Cristina ; Davis, Shelly ; Bellora, Nicolás ; Gallardo, Fernando ; López-Arribillaga, Erika ; Asensio-Juan, Elena ; Rodilla, Verónica ; González, Jessica ; Iglesias, Mar ; Shih, Vincent ; Mar Albà, M. ; Di Croce, Luciano ; Hoffmann, Alexander ; Miyamoto, Shigeki ; Villà-Freixa, Jordi ; López-Bigas, Nuria ; Keyes, William M. ; Domínguez, María ; Bigas, Anna ; Espinosa, Lluís</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-defe695374ea69e14669ca62bdfad4976f3883f7ff8fbd943dbe685c36e7a13f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Cell Differentiation - 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Here, we demonstrate that sumoylated and phosphorylated IκBα accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chromatin-bound IκBα modulates Polycomb recruitment and imparts their competence to be activated by TNFα. Mutations in the Drosophila IκBα gene cactus enhance the homeotic phenotype of Polycomb mutants, which is not counteracted by mutations in dorsal/NF-κB. Oncogenic transformation of keratinocytes results in cytoplasmic IκBα translocation associated with a massive activation of Hox. Accumulation of cytoplasmic IκBα was found in squamous cell carcinoma (SCC) associated with IKK activation and HOX upregulation.
[Display omitted]
•Sumoylated and phosphorylated IκBα binds H2A and H4 in keratinocytes•IκBα regulates keratinocyte differentiation and transformation•IκBα regulates Polycomb chromatin release and HOX expression in response to TNFα•IκBα cooperates with Polycomb in Drosophila patterning</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23850221</pmid><doi>10.1016/j.ccr.2013.06.003</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1535-6108 |
| ispartof | Cancer cell, 2013-08, Vol.24 (2), p.151-166 |
| issn | 1535-6108 1878-3686 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3962677 |
| source | MEDLINE; Recercat; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Cell Differentiation - genetics Cell Nucleus - genetics Cell Nucleus - metabolism Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Cell Transformation, Neoplastic - pathology Chromatin - genetics Chromatin - metabolism Cèl·lules Drosophila HEK293 Cells Histones - genetics Histones - metabolism Humans I-kappa B Proteins - genetics I-kappa B Proteins - metabolism Keratinocytes - cytology Keratinocytes - metabolism Mice Mice, Inbred C57BL NF-KappaB Inhibitor alpha Pell Signal Transduction Skin Neoplasms - genetics Skin Neoplasms - metabolism Skin Neoplasms - pathology Tumors |
| title | Chromatin-Bound IκBα Regulates a Subset of Polycomb Target Genes in Differentiation and Cancer |
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