Cisinteractions in theIrf8locus regulate stage-dependent enhancer activation
العنوان: | Cisinteractions in theIrf8locus regulate stage-dependent enhancer activation |
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المؤلفون: | Tian-Tian Liu, Feiya Ou, Julia A. Belk, Prachi Bagadia, David A. Anderson, Vivek Durai, Winnie Yao, Ansuman T. Satpathy, Theresa L. Murphy, Kenneth M. Murphy |
المصدر: | Genes & Development. 37:291-302 |
بيانات النشر: | Cold Spring Harbor Laboratory, 2023. |
سنة النشر: | 2023 |
مصطلحات موضوعية: | Genetics, Developmental Biology |
الوصف: | Individual elements within a superenhancer can act in a cooperative or temporal manner, but the underlying mechanisms remain obscure. We recently identified anIrf8superenhancer, within which different elements act at distinct stages of type 1 classical dendritic cell (cDC1) development. The +41-kbIrf8enhancer is required for pre-cDC1 specification, while the +32-kbIrf8enhancer acts to support subsequent cDC1 maturation. Here, we found that compound heterozygous Δ32/Δ41 mice, lacking the +32- and +41-kb enhancers on different chromosomes, show normal pre-cDC1 specification but, surprisingly, completely lack mature cDC1 development, suggestingcisdependence of the +32-kb enhancer on the +41-kb enhancer. Transcription of the +32-kbIrf8enhancer-associated long noncoding RNA (lncRNA) Gm39266 is also dependent on the +41-kb enhancer. However, cDC1 development in mice remained intact when Gm39266 transcripts were eliminated by CRISPR/Cas9-mediated deletion of lncRNA promoters and when transcription across the +32-kb enhancer was blocked by premature polyadenylation. We showed that chromatin accessibility and BATF3 binding at the +32-kb enhancer were dependent on a functional +41-kb enhancer located incis. Thus, the +41-kbIrf8enhancer controls the subsequent activation of the +32-kbIrf8enhancer in a manner that is independent of associated lncRNA transcription. |
تدمد: | 1549-5477 0890-9369 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::cc2f074d58bcd55b86e8139591923298 https://doi.org/10.1101/gad.350339.122 |
رقم الأكسشن: | edsair.doi...........cc2f074d58bcd55b86e8139591923298 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15495477 08909369 |
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