Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.05.238253v1?rss=1 Authors: Daly, A. Z., Dudley, L. A., Peel, M. T., Liebhaber, S. A., Parker, S. C., Camper, S. A. Abstract: Pituitary thyrotropes are specialized cells that produce thyroid stimulating hormone, a critical factor for growth and maintenance of metabolism. The transcription factors POU1F1 and GATA2 have been implicated in thyrotrope fate and regulation of Tshb transcription, but no transcriptomic or epigenetic analyses of these cells has been undertaken. The goal of this work was to discover key elements that drive thyrotrope fate. We identified the transcription factors and epigenetic changes in chromatin that are associated with differentiation of POU1F1-expressing progenitors into thyrotropes using cell lines that represent an early, undifferentiated Pou1f1 lineage progenitor (GHF-T1) or a committed thyrotrope (TT1). We generated and integrated genome-wide information about DNA accessibility, histone modification, POU1F1 transcription factor binding and RNA expression data to identify regulatory elements and candidate transcriptional regulators. We identified POU1F1 binding sites that were unique to each cell line. POU1F1 binding sites are commonly associated with bZIP transcription factor consensus binding sites in GHF-T1 cells and HLH (Helix-Turn-Helix) or basic Helix-Turn-Helix (bHLH) factors in TT1 cells, suggesting that some classes of transcription factors may recruit or cooperate with POU1F1 binding to unique sites. We validated enhancer function of novel elements we mapped near Cga, Pitx1, Gata2, and Tshb by transfection in TT1 cells. Finally, we confirmed that an enhancer element near Tshb can drive expression in thyrotropes of transgenic mice, and we demonstrate that GATA2 enhances Tshb expression through this element. These data extend the ENCODE analysis to an organ that is critical for growth and metabolism. This information may be valuable for understanding pituitary development and disease pathogenesis. Copy rights belong to original authors. Visit the link for more info