Mechanisms of Transcription Factor Yin Yang 1

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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.