Mechanisms of Transcription Factor Yin Yang 1

描述（由申请人提供）：序列特异性dna结合转录因子在许多发育过程和细胞行为控制中发挥关键作用。阴阳1 （YY1）是一种41 -氨基酸的kruppel相关锌指转录因子，与位于许多细胞和病毒基因的启动子和增强子中的CGCCATNTT共识DNA元件结合。像许多转录因子一样，YY1需要辅激活因子和辅抑制因子才能正常工作。有趣的是，YY1作为激活剂和抑制剂似乎同样有效，这取决于它的相对浓度、结合伙伴和启动子环境。尽管关于可能受YY1调控的基因数量的报道不断增加，但该因子调控转录的确切机制仍不清楚。该提案的长期目标是对YY1调控转录的机制有更深入的了解。先前的研究表明YY1与组蛋白乙酰转移酶（HATs）和组蛋白去乙酰化酶（HDACs）相互作用。目前提出的研究侧重于YY1-HATs和yy1 - hdac相互作用的功能意义的详细分析。有待探索的假设是，YY1至少有部分作用是它与HATs和hdac接触的结果，这允许HATs或hdac的募集来酶修饰组蛋白，从而影响转录。我们将研究另一种非互排斥的假设，即HATs或hdac与YY1之间的相互作用改变YY1的乙酰化状态，从而改变YY1的活性。最后，在体内对YY1与HATs或hdac联合调控的基因进行严格的鉴定和表征。考虑到YY1可能控制的一长串基因，毫无疑问，这个因子为转录调控的研究提供了一个有吸引力的模型，通过彻底了解YY1的活性是如何被调控的，可以获得巨大的好处。这些研究不仅从根本上有助于更好地理解基因调控的分子生物学，而且还将为许多生理上重要基因的精确控制提供关键的见解。

DESCRIPTION (provided by applicant): Sequence-specific DNA-binding transcription factors play pivotal roles in many developmental processes and in the control of cell behavior. Yin Yang 1 (YY1) is a 41 4-amino-acid Kruppel-related zinc finger transcription factor that binds to the CGCCATNTT consensus DNA element located in promoters and enhancers of many cellular and viral genes. Like many transcription factors, YY1 requires coactivators and corepressors to function properly. Interestingly, YY1 appears to be equally effective as an activator and as a repressor depending on its relative concentration, its binding partners, and on promoter context. Although reports of the number of genes that might be regulated by YY1 are ever increasing, the exact mechanisms by which this factor regulates transcription are still unclear. The long-term goal of this proposal is aimed at obtaining a greater mechanistic understanding of how YY1 regulates transcription. Previous studies indicate that YY1 interacts with histone acetyltransferases (HATs) and with histone deacetylases (HDACs). The current proposed study focuses on a detailed analysis of the functional significance of the YY1-HATs and YY1-HDACs interactions. The hypothesis to be explored is that at least some of the effects of YY1 are a result of its contact with HATs and with HDACs, which allows the recruitment of HATs or HDACs to enzymatically modify histones and consequently affect transcription. An alternative, non-mutually exclusive hypothesis will be examined in which the interaction between HATs or HDACs and YY1 modifies the acetylation status of YY1 and consequently alters YY1s activity. Finally, genes that are regulated by YY1 in combination with HATs or HDACs in vivo will be rigorously identified and characterized. Given the long list of genes that could potentially be controlled by YY1, there is no dispute that this factor provides an attractive model for the study of transcriptional regulation and that enormous benefits can be gained by thoroughly understanding how the activity of YY1 is regulated. These studies will not only contribute fundamentally to a better understanding of the molecular biology of gene regulation but will also provide critical insights regarding the precise control of many physiologically important genes.