Norris Cotton Cancer Center, Institute for Quantitative Biomedical Sciences, Department of Genetics, Dartmouth Medical School, Lebanon, NH 03756, USA.
Trends Genet. 2011 Nov;27(11):465-74. doi: 10.1016/j.tig.2011.07.002. Epub 2011 Aug 30.
Chromatin is a well-known obstacle to transcription as it controls DNA accessibility, which directly impacts the recruitment of the transcriptional machinery. The recent burst of functional genomic studies provides new clues as to how transcriptional competency is regulated in this context. In this review, we discuss how these studies have shed light on a specialized subset of transcription factors, defined as pioneer factors, which direct recruitment of downstream transcription factors to establish lineage-specific transcriptional programs. In particular, we present evidence of an interplay between pioneer factors and the epigenome that could be central to this process. Finally, we discuss how pioneer factors, whose expression and function are altered in tumors, are also being considered for their prognostic value and should therefore be regarded as potential therapeutic targets. Thus, pioneer factors emerge as key players that connect the epigenome and transcription in health and disease.
染色质是转录的众所周知的障碍，因为它控制 DNA 的可及性，这直接影响转录机制的募集。最近功能基因组研究的爆发为我们提供了新的线索，了解在这种情况下转录能力是如何被调控的。在这篇综述中，我们讨论了这些研究如何揭示了一类特殊的转录因子，即先驱因子，它们指导下游转录因子的募集，以建立谱系特异性的转录程序。特别是，我们提出了先驱因子与表观基因组之间相互作用的证据，这可能是这个过程的核心。最后，我们讨论了在肿瘤中表达和功能发生改变的先驱因子，它们也因其预后价值而被考虑，因此应该被视为潜在的治疗靶点。因此，先驱因子成为连接健康和疾病中表观基因组和转录的关键因素。
