Parabiosis experiments demonstrating that dendritic cells (DCs) do not equilibrate between mice even after prolonged joining by parabiosis have suggested that DCs are derived from self-renewing progenitors that divide in situ. However, here we found that unequal exchange of DCs between mice joined by parabiosis reflected uneven distribution of DC precursors in blood due to their short half-life in circulation. DCs underwent only a limited number of divisions in the spleen or lymph nodes over a 10- to 14-day period and were replenished from blood-borne precursors at a rate of nearly 4,300 cells per hour. Daughter DCs presented antigens captured by their progenitors, suggesting that DC division in peripheral lymphoid organs can prolong the duration of antigen presentation in vivo.

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In prostate cancer, androgen receptor (AR) binding and androgen-responsive gene expression are defined by hormone-independent binding patterns of the pioneer factors FoxA1 and GATA2. Insufficient evidence of the mechanisms by which GATA2 contributes to this process precludes complete understanding of a key determinant of tissue-specific AR activity. Our observations suggest that GATA2 facilitates androgen-responsive gene expression by three distinct modes of action. By occupying novel binding sites within the AR gene locus, GATA2 positively regulates AR expression before and after androgen stimulation. Additionally, GATA2 engages AR target gene enhancers prior to hormone stimulation, producing an active and accessible chromatin environment via recruitment of the histone acetyltransferase p300. Finally, GATA2 functions in establishing and/or sustaining basal locus looping by recruiting the Mediator subunit MED1 in the absence of androgen. These mechanisms may contribute to the generally positive role of GATA2 in defining AR genome-wide binding patterns that determine androgen-responsive gene expression profiles. We also find that GATA2 and FoxA1 exhibit both independent and codependent co-occupancy of AR target gene enhancers. Identifying these determinants of AR transcriptional activity may provide a foundation for the development of future prostate cancer therapeutics that target pioneer factor function.