TrxG complexes in pancreas endocrine-cell specification

转录调控是胰腺谱系特化和成熟的关键组成部分。尽管如此，参与这一过程的转录因子调节的具体机制还不清楚。表观遗传因素，包括DNA甲基化和组蛋白修饰是转录调控的中心介质。我们以前的数据表明，内分泌和外分泌谱系定型所必需的许多转录因子需要获得活性染色质状态，和/或去除抑制性组蛋白修饰才能表达。我们假设这些变化是由三胸组（TrxG）复合物催化的。TrxG复合物都含有核心蛋白Ash 21、Dpy 30、Rbbp 5和Wdr 5，这些蛋白对其组装和/或功能至关重要。因此，为了检验我们的假设，即该复合物对于诱导内分泌和外分泌谱系定型所必需的转录因子是必需的，我们敲除了胰腺祖细胞中的核心组分Dpy 30。我们的初步数据表明，在这些小鼠中，胰腺祖细胞分化为内分泌和外分泌谱系受到严重影响。

Transcriptional regulation is a critical component of pancreas lineage specification and maturation. Despite this the specific mechanisms by which transcription factors involved in this process are regulate are not well understood. Epigenetic factors, which include DNA methylation and histone modifications are central mediators of transcriptional regulation. Our previous data indicated that many of the transcription factors necessary for endocrine and exocrine lineage commitment need to gain an active chromatin state, and/or to remove repressive histone modifications to become expressed. We hypothesized that these changes were catalyzed by trithorax group (TrxG) complexes. TrxG complexes all contain the core proteins Ash2l, Dpy30, Rbbp5, and Wdr5 that are critical to their assembly and/or function. Thus to test our hypothesis that this complex was necessary for the induction of transcription factors necessary for endocrine and exocrine lineage commitment we knocked-out the core component Dpy30 in pancreas progenitors. Our preliminary data suggests that in these mice specification of pancreas progenitors into both endocrine and exocrine lineages is severely compromised.