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Core promoter recognition complex changes accompany liver development

机译:核心启动子识别复合物变化伴随肝脏发育

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摘要

Recent studies of several key developmental transitions have brought into question the long held view of the basal transcriptional apparatus as ubiquitous and invariant. In an effort to better understand the role of core promoter recognition and coactivator complex switching in cellular differentiation, we have examined changes in transcription factor IID (TFIID) and cofactor required for Sp1 activation/Mediator during mouse liver development. Here we show that the differentiation of fetal liver progenitors to adult hepatocytes involves a wholesale depletion of canonical cofactor required for Sp1 activation/Mediator and TFIID complexes at both the RNA and protein level, and that this alteration likely involves silencing of transcription factor promoters as well as protein degradation. It will be intriguing for future studies to determine if a novel and as yet unknown core promoter recognition complex takes the place of TFIID in adult hepatocytes and to uncover the mechanisms that down-regulate TFIID during this critical developmental transition.
机译:对几种关键的发育过渡的最新研究使人们一直对基础转录装置无处不在且不变的观点持怀疑态度。为了更好地理解核心启动子识别和共激活因子复合物转换在细胞分化中的作用,我们研究了小鼠肝脏发育过程中转录因子IID(TFIID)和Sp1激活/介体所需的辅因子的变化。在这里,我们显示胎儿肝祖细胞向成年肝细胞的分化涉及在RNA和蛋白质水平上Sp1激活/介体和TFIID复合体所需的典型辅因子的整体消耗,并且这种改变也可能使转录因子启动子沉默作为蛋白质降解。未来的研究将确定一种新颖的,至今仍未知的核心启动子识别复合物是否能替代成人肝细胞中的TFIID,并揭示在这一关键的发育过渡过程中下调TFIID的机制,这将是令人感兴趣的。

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