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Cryptic activation of an Irf8 enhancer governs cDC1 fate specification
Induction of the transcription factor Irf8 in the common dendritic cell progenitor (CDP) is required for classical type 1 dendritic cell (cDC1) fate specification, but the mechanisms controlling this induction are unclear. Here we identified Irf8 enhancers via chromatin profiling of DCs and used CRI...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2019
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707878/ https://www.ncbi.nlm.nih.gov/pubmed/31406378 http://dx.doi.org/10.1038/s41590-019-0450-x |
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| author | Durai, Vivek Bagadia, Prachi Granja, Jeffrey M. Satpathy, Ansuman T. Kulkarni, Devesha H. Davidson, Jesse T. Wu, Renee Patel, Swapneel J. Iwata, Arifumi Liu, Tiantian Huang, Xiao Briseño, Carlos G. Grajales-Reyes, Gary E. Wöhner, Miriam Tagoh, Hiromi Kee, Barbara L. Newberry, Rodney D. Busslinger, Meinrad Chang, Howard Y. Murphy, Theresa L. Murphy, Kenneth M. |
| author_facet | Durai, Vivek Bagadia, Prachi Granja, Jeffrey M. Satpathy, Ansuman T. Kulkarni, Devesha H. Davidson, Jesse T. Wu, Renee Patel, Swapneel J. Iwata, Arifumi Liu, Tiantian Huang, Xiao Briseño, Carlos G. Grajales-Reyes, Gary E. Wöhner, Miriam Tagoh, Hiromi Kee, Barbara L. Newberry, Rodney D. Busslinger, Meinrad Chang, Howard Y. Murphy, Theresa L. Murphy, Kenneth M. |
| author_sort | Durai, Vivek |
| collection | PubMed |
| description | Induction of the transcription factor Irf8 in the common dendritic cell progenitor (CDP) is required for classical type 1 dendritic cell (cDC1) fate specification, but the mechanisms controlling this induction are unclear. Here we identified Irf8 enhancers via chromatin profiling of DCs and used CRISPR/Cas9 genome editing to assess their roles in Irf8 regulation. An enhancer 32 kilobases downstream of the Irf8 transcriptional start site (+32 kb Irf8) that was active in mature cDC1s was required for the development of this lineage, but not for its specification. Instead, a +41 kb Irf8 enhancer previously thought to be active only in plasmacytoid DCs was found to also be transiently accessible in cDC1 progenitors, and deleting this enhancer prevented the induction of Irf8 in CDPs and abolished cDC1 specification. Thus, cryptic activation of the +41 kb Irf8 enhancer in DC progenitors is responsible for cDC1 fate specification. |
| format | Online Article Text |
| id | pubmed-6707878 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-67078782020-02-12 Cryptic activation of an Irf8 enhancer governs cDC1 fate specification Durai, Vivek Bagadia, Prachi Granja, Jeffrey M. Satpathy, Ansuman T. Kulkarni, Devesha H. Davidson, Jesse T. Wu, Renee Patel, Swapneel J. Iwata, Arifumi Liu, Tiantian Huang, Xiao Briseño, Carlos G. Grajales-Reyes, Gary E. Wöhner, Miriam Tagoh, Hiromi Kee, Barbara L. Newberry, Rodney D. Busslinger, Meinrad Chang, Howard Y. Murphy, Theresa L. Murphy, Kenneth M. Nat Immunol Article Induction of the transcription factor Irf8 in the common dendritic cell progenitor (CDP) is required for classical type 1 dendritic cell (cDC1) fate specification, but the mechanisms controlling this induction are unclear. Here we identified Irf8 enhancers via chromatin profiling of DCs and used CRISPR/Cas9 genome editing to assess their roles in Irf8 regulation. An enhancer 32 kilobases downstream of the Irf8 transcriptional start site (+32 kb Irf8) that was active in mature cDC1s was required for the development of this lineage, but not for its specification. Instead, a +41 kb Irf8 enhancer previously thought to be active only in plasmacytoid DCs was found to also be transiently accessible in cDC1 progenitors, and deleting this enhancer prevented the induction of Irf8 in CDPs and abolished cDC1 specification. Thus, cryptic activation of the +41 kb Irf8 enhancer in DC progenitors is responsible for cDC1 fate specification. 2019-08-12 2019-09 /pmc/articles/PMC6707878/ /pubmed/31406378 http://dx.doi.org/10.1038/s41590-019-0450-x Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Durai, Vivek Bagadia, Prachi Granja, Jeffrey M. Satpathy, Ansuman T. Kulkarni, Devesha H. Davidson, Jesse T. Wu, Renee Patel, Swapneel J. Iwata, Arifumi Liu, Tiantian Huang, Xiao Briseño, Carlos G. Grajales-Reyes, Gary E. Wöhner, Miriam Tagoh, Hiromi Kee, Barbara L. Newberry, Rodney D. Busslinger, Meinrad Chang, Howard Y. Murphy, Theresa L. Murphy, Kenneth M. Cryptic activation of an Irf8 enhancer governs cDC1 fate specification |
| title | Cryptic activation of an Irf8 enhancer governs cDC1 fate specification |
| title_full | Cryptic activation of an Irf8 enhancer governs cDC1 fate specification |
| title_fullStr | Cryptic activation of an Irf8 enhancer governs cDC1 fate specification |
| title_full_unstemmed | Cryptic activation of an Irf8 enhancer governs cDC1 fate specification |
| title_short | Cryptic activation of an Irf8 enhancer governs cDC1 fate specification |
| title_sort | cryptic activation of an irf8 enhancer governs cdc1 fate specification |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707878/ https://www.ncbi.nlm.nih.gov/pubmed/31406378 http://dx.doi.org/10.1038/s41590-019-0450-x |
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