We describe a broad mechanistic framework for the transcriptional induction of mammalian primary response genes by Toll-like receptors and other stimuli. One major class of primary response genes is characterized by CpG-island promoters, which facilitate promiscuous induction from constitutively active chromatin without a requirement for SWI/SNF nucleosome remodeling complexes. The low nucleoso...

Much effort in cancer research has focused on the tiny part of our genome that codes for mRNA. However, it has recently been recognized that microRNAs also contribute decisively to tumorigenesis. Studies have also shown that epigenetic silencing by CpG island hypermethylation of microRNAs with tumor suppressor activities is a common feature of human cancer. The importance of other classes of no...

The p21 belongs to the CIP/KIP family of CDK inhibitors involved in cell cycle arrest at specific stages of the cell cycle progression. DNA methylation is the best studied epigenetic mark that have been evidently associated to chromatin condensation, and repression of gene transcription. The CpG island hypermethylation in promoter region of certain genes occurs in cancer cells and affects tumor...

Recent analyses of global and gene-specific methylation patterns in cancer cells have suggested that cancers from different organs demonstrate distinct patterns of CpG island hypermethylation. Although certain CpG islands are frequently methylated in many different kinds of cancer, others are methylated only in specific tumor types. Because distinct patterns of CpG island hypermethylation can b...

GC skew is a measure of the strand asymmetry in the distribution of guanines and cytosines. GC skew favors R-loops, a type of three stranded nucleic acid structures that form upon annealing of an RNA strand to one strand of DNA, creating a persistent RNA:DNA hybrid. Previous studies show that GC skew is prevalent at thousands of human CpG island (CGI) promoters and transcription termination reg...

It is well established that DNA hypermethylation of tumor suppressor and tumor-related genes can occur in cancer cells and that each cancer subtype has specific gene sets that are commonly susceptible to methylation and silencing. Glutathione S-transferase (GSTP1) is one example of a gene that is hypermethylated and inactivated in the majority of prostate cancers. We previously reported that hy...

Regulatory T cells (T reg cells) are a population of CD4+ T cells that limit immune responses. FoxP3 is a master control transcription factor for development and function of these cells, but its regulation is poorly understood. We have identified a T cell receptor-responsive enhancer in the FoxP3 first intron that is dependent on a cyclic-AMP response element binding protein (CREB)/activating t...

Epigenetic silencing associated with aberrant methylation of promoter region CpG islands is one mechanism leading to loss of tumor suppressor function in human cancer. Profiling of CpG island methylation indicates that some genes are more frequently methylated than others, and that each tumor type is associated with a unique set of methylated genes. However, little is known about why certain ge...

CpG island methylator phenotype of breast cancer is associated with widespread aberrant methylation at specified CpG islands and distinct patient outcomes. However, the influence of copy number contributing to the prognosis of tumors with different CpG island methylator phenotypes is still unclear. We analyzed both genetic (copy number) and epigenetic alterations in 765 breast cancers from The ...