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Publication : Transition from cMyc to L-Myc during dendritic cell development coordinated by rising levels of IRF8.

First Author  Anderson DA Year  2022
Journal  J Exp Med Volume  219
Issue  2 PubMed ID  34958351
Mgi Jnum  J:329864 Mgi Id  MGI:7314151
Doi  10.1084/jem.20211483 Citation  Anderson DA, et al. (2022) Transition from cMyc to L-Myc during dendritic cell development coordinated by rising levels of IRF8. J Exp Med 219(2):e20211483
abstractText  During dendritic cell (DC) development, Myc expression in progenitors is replaced by Mycl in mature DCs, but when and how this transition occurs is unknown. We evaluated DC development using reporters for MYC, MYCL, and cell cycle proteins Geminin and CDT1 in wild-type and various mutant mice. For classical type 1 dendritic cells (cDC1s) and plasmacytoid DCs (pDCs), the transition occurred upon their initial specification from common dendritic cell progenitors (CDPs) or common lymphoid progenitors (CLPs), respectively. This transition required high levels of IRF8 and interaction with PU.1, suggesting the use of EICEs within Mycl enhancers. In pDCs, maximal MYCL induction also required the +41kb Irf8 enhancer that controls pDC IRF8 expression. IRF8 also contributed to repression of MYC. While MYC is expressed only in rapidly dividing DC progenitors, MYCL is most highly expressed in DCs that have exited the cell cycle. Thus, IRF8 levels coordinate the Myc-Mycl transition during DC development.
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