| Literature DB >> 27986456 |
Lucja T Grajkowska1, Michele Ceribelli2, Colleen M Lau3, Margaret E Warren4, Ioanna Tiniakou3, Sandra Nakandakari Higa3, Anna Bunin5, Hans Haecker6, Leonid A Mirny7, Louis M Staudt8, Boris Reizis9.
Abstract
The cell fate decision between interferon-producing plasmacytoid DC (pDC) and antigen-presenting classical DC (cDC) is controlled by the E protein transcription factor TCF4 (E2-2). We report that TCF4 comprises two transcriptional isoforms, both of which are required for optimal pDC development in vitro. The long Tcf4 isoform is expressed specifically in pDCs, and its deletion in mice impaired pDCs development and led to the expansion of non-canonical CD8+ cDCs. The expression of Tcf4 commenced in progenitors and was further upregulated in pDCs, correlating with stage-specific activity of multiple enhancer elements. A conserved enhancer downstream of Tcf4 was required for its upregulation during pDC differentiation, revealing a positive feedback loop. The expression of Tcf4 and the resulting pDC differentiation were selectively sensitive to the inhibition of enhancer-binding BET protein activity. Thus, lineage-specifying function of E proteins is facilitated by lineage-specific isoform expression and by BET-dependent feedback regulation through distal regulatory elements.Entities:
Keywords: E proteins; dendritic cells; enhancers; feedback regulation; plasmacytoid dendritic cells; transcription factors
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Year: 2016 PMID： 27986456 PMCID： PMC5243153 DOI： 10.1016/j.immuni.2016.11.006
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745