Analysis method of epigenetic DNA methylation to dynamically investigate the functional activity of transcription factors in gene expression

Abstract

BackgroundDNA methylation is a fundamental component of epigenetic modification, which is intimately involved in the regulation of gene expression. One important DNA methylation pathway reduces the abilities of transcription factors to bind to gene promoter regions. Although many experiments have been designed to measure genome-wide DNA methylation levels at high resolution, the meaning of these different DNA methylation levels on transcription factor binding abilities remains poorly understood. We have, therefore, developed a method to quantitatively explore the extent to which DNA methylation levels can significantly reduce or even abolish the binding of certain transcription factors, resulting in reduced or non-expression of flanking genes. This method allows transcription factors that are functionally active in gene expression to be investigated.ResultsThe method is based on a general model that depicts the relationship between DNA methylation and transcription factor binding ability based on intrinsic component properties, and the model parameters can be optimized through relative analysis of recognized transcription factor binding status and gene expression profiling. With fixed models, transcription factors functionally active in the regulation of gene expression and affected by epigenetic DNA methylation can be identified and subsequently confirmed. The method identified eleven apparently functionally active transcriptional factors in SH-SY5Y neuroblastoma cells.ConclusionsCompared with gene regulatory elements, epigenetic modifications are able to change to dynamically respond to signals from physical, biological and social environments. Our proposed method is therefore designed to provide a dynamic assessment to investigate functionally active transcription factors. With the information deduced from our method, we can predict transcription factor binding status in promoter regions to further investigate how a particular gene is regulated by a specific group of transcription factors organized in a particular pattern. This will be helpful in the diagnosis and development of treatment for numerous diseases, including cancer. Although the method only investigates DNA methylation, it has the potential to be applied to more epigenetic factors, such as histone modification.