The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells
Invariant natural killer T cells (iNKT cells) are innate-like lymphocytes that protect against infection, autoimmune disease and cancer. However, little is known about the epigenetic regulation of iNKT cell development. Here we found that the H3K27me3 histone demethylase UTX was an essential cell-in...
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| Format: | Article |
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Springer Nature
2018
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| Online Access: | http://hdl.handle.net/1721.1/117007 https://orcid.org/0000-0002-7577-4612 |
| _version_ | 1811003189181284352 |
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| author | Beyaz, Semir Kim, Ji Hyung Pinello, Luca Huang, Jialiang Kerenyi, Marc A Das, Partha P Barnitz, R Anthony Herault, Aurelie Haining, W Nicholas Passegue, Emmanuelle Yuan, Guo-Cheng Orkin, Stuart H Winau, Florian Xifaras, Michael Dogum, Rizkullah Yilmaz, Omer Hu, Yu,M.C.P.Massachusetts Institute of Technology. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Beyaz, Semir Kim, Ji Hyung Pinello, Luca Huang, Jialiang Kerenyi, Marc A Das, Partha P Barnitz, R Anthony Herault, Aurelie Haining, W Nicholas Passegue, Emmanuelle Yuan, Guo-Cheng Orkin, Stuart H Winau, Florian Xifaras, Michael Dogum, Rizkullah Yilmaz, Omer Hu, Yu,M.C.P.Massachusetts Institute of Technology. |
| author_sort | Beyaz, Semir |
| collection | MIT |
| description | Invariant natural killer T cells (iNKT cells) are innate-like lymphocytes that protect against infection, autoimmune disease and cancer. However, little is known about the epigenetic regulation of iNKT cell development. Here we found that the H3K27me3 histone demethylase UTX was an essential cell-intrinsic factor that controlled an iNKT-cell lineage-specific gene-expression program and epigenetic landscape in a demethylase-Activity-dependent manner. UTX-deficient iNKT cells exhibited impaired expression of iNKT cell signature genes due to a decrease in activation-Associated H3K4me3 marks and an increase in repressive H3K27me3 marks within the promoters occupied by UTX. We found that JunB regulated iNKT cell development and that the expression of genes that were targets of both JunB and the iNKT cell master transcription factor PLZF was UTX dependent. We identified iNKT cell super-enhancers and demonstrated that UTX-mediated regulation of super-enhancer accessibility was a key mechanism for commitment to the iNKT cell lineage. Our findings reveal how UTX regulates the development of iNKT cells through multiple epigenetic mechanisms. |
| first_indexed | 2024-09-23T16:00:28Z |
| format | Article |
| id | mit-1721.1/117007 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:00:28Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | mit-1721.1/1170072022-10-02T05:42:58Z The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells Beyaz, Semir Kim, Ji Hyung Pinello, Luca Huang, Jialiang Kerenyi, Marc A Das, Partha P Barnitz, R Anthony Herault, Aurelie Haining, W Nicholas Passegue, Emmanuelle Yuan, Guo-Cheng Orkin, Stuart H Winau, Florian Xifaras, Michael Dogum, Rizkullah Yilmaz, Omer Hu, Yu,M.C.P.Massachusetts Institute of Technology. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Xifaras, Michael Dogum, Rizkullah Yilmaz, Omer Invariant natural killer T cells (iNKT cells) are innate-like lymphocytes that protect against infection, autoimmune disease and cancer. However, little is known about the epigenetic regulation of iNKT cell development. Here we found that the H3K27me3 histone demethylase UTX was an essential cell-intrinsic factor that controlled an iNKT-cell lineage-specific gene-expression program and epigenetic landscape in a demethylase-Activity-dependent manner. UTX-deficient iNKT cells exhibited impaired expression of iNKT cell signature genes due to a decrease in activation-Associated H3K4me3 marks and an increase in repressive H3K27me3 marks within the promoters occupied by UTX. We found that JunB regulated iNKT cell development and that the expression of genes that were targets of both JunB and the iNKT cell master transcription factor PLZF was UTX dependent. We identified iNKT cell super-enhancers and demonstrated that UTX-mediated regulation of super-enhancer accessibility was a key mechanism for commitment to the iNKT cell lineage. Our findings reveal how UTX regulates the development of iNKT cells through multiple epigenetic mechanisms. 2018-07-19T17:07:50Z 2018-07-19T17:07:50Z 2017-02 2018-07-13T16:13:01Z Article http://purl.org/eprint/type/JournalArticle 1529-2908 1529-2916 http://hdl.handle.net/1721.1/117007 Beyaz, Semir, et al. “The Histone Demethylase UTX Regulates the Lineage-Specific Epigenetic Program of Invariant Natural Killer T Cells.” Nature Immunology, vol. 18, no. 2, Dec. 2016, pp. 184–95. https://orcid.org/0000-0002-7577-4612 http://dx.doi.org/10.1038/NI.3644 Nature Immunology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Nature PMC |
| spellingShingle | Beyaz, Semir Kim, Ji Hyung Pinello, Luca Huang, Jialiang Kerenyi, Marc A Das, Partha P Barnitz, R Anthony Herault, Aurelie Haining, W Nicholas Passegue, Emmanuelle Yuan, Guo-Cheng Orkin, Stuart H Winau, Florian Xifaras, Michael Dogum, Rizkullah Yilmaz, Omer Hu, Yu,M.C.P.Massachusetts Institute of Technology. The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells |
| title | The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells |
| title_full | The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells |
| title_fullStr | The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells |
| title_full_unstemmed | The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells |
| title_short | The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells |
| title_sort | histone demethylase utx regulates the lineage specific epigenetic program of invariant natural killer t cells |
| url | http://hdl.handle.net/1721.1/117007 https://orcid.org/0000-0002-7577-4612 |
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