@article {2131,
	title = {Direct, androgen receptor-mediated regulation of the FKBP5 gene via a distal enhancer element.},
	journal = {Endocrinology},
	volume = {147},
	year = {2006},
	month = {2006 Jan 6},
	pages = {590-8},
	abstract = {<p>Androgen signaling via the androgen receptor (AR) transcription factor is crucial to normal prostate homeostasis and prostate tumorigenesis. Current models of AR function are predominantly based on studies of prostate-specific antigen regulation in androgen-responsive cell lines. To expand on these in vitro paradigms, we used the mouse prostate to elucidate the mechanisms through which AR regulates another direct target, FKBP5, in vivo. FKBP5 encodes an immunophilin that has been previously implicated in glucocorticoid and progestin signaling pathways and that likely influences prostate physiology in the presence of androgens. In this work, we show that androgens directly regulate FKBP5 via an interaction between the AR and a distal enhancer located 65 kb downstream of the transcription start site in the fifth intron of the FKBP5 gene. We have found that AR selectively recruits cAMP response element-binding protein to this enhancer. These interactions, in turn, result in chromatin remodeling that affects the enhancer proper but not the FKBP5 locus as a whole. Furthermore, in contrast to prostate-specific antigen-regulatory mechanisms, we show that transactivation of the FKBP5 gene does not rely on a single looping complex to mediate communication between the distal enhancer and proximal promoter. Rather, the distal enhancer complex and basal transcription apparatus communicate indirectly with one another, implicating a regulatory mechanism that has not been previously appreciated for AR target genes.</p>
},
	keywords = {Androgen, Animals, Base Sequence, Chromosome Mapping, Conserved Sequence, Enhancer Elements, Gene Expression Regulation, Genetic, Humans, Introns, Male, Mice, Molecular Sequence Data, Nucleic Acid, Orchiectomy, Prostate, Receptors, Reverse Transcriptase Polymerase Chain Reaction, Sequence Alignment, Sequence Homology, Tacrolimus Binding Proteins, Transcription},
	issn = {0013-7227},
	doi = {10.1002/cbic.201000254},
	author = {Magee, Jeffrey A and Chang, Li-Wei and Stormo, Gary D and Milbrandt, Jeffrey}
}
@article {2129,
	title = {A systematic model to predict transcriptional regulatory mechanisms based on overrepresentation of transcription factor binding profiles.},
	journal = {Genome Research},
	volume = {16},
	year = {2006},
	month = {2006 Mar},
	pages = {405-13},
	abstract = {<p>An important aspect of understanding a biological pathway is to delineate the transcriptional regulatory mechanisms of the genes involved. Two important tasks are often encountered when studying transcription regulation, i.e., (1) the identification of common transcriptional regulators of a set of coexpressed genes; (2) the identification of genes that are regulated by one or several transcription factors. In this study, a systematic and statistical approach was taken to accomplish these tasks by establishing an integrated model considering all of the promoters and characterized transcription factors (TFs) in the genome. A promoter analysis pipeline (PAP) was developed to implement this approach. PAP was tested using coregulated gene clusters collected from the literature. In most test cases, PAP identified the transcription regulators of the input genes accurately. When compared with chromatin immunoprecipitation experiment data, PAP{\textquoteright}s predictions are consistent with the experimental observations. When PAP was used to analyze one published expression-profiling data set and two novel coregulated gene sets, PAP was able to generate biologically meaningful hypotheses. Therefore, by taking a systematic approach of considering all promoters and characterized TFs in our model, we were able to make more reliable predictions about the regulation of gene expression in mammalian organisms.</p>
},
	keywords = {Animals, Cell Proliferation, Cholesterol, Chromatin Immunoprecipitation, Computational Biology, Conserved Sequence, Gene Expression Profiling, Gene Expression Regulation, Genetic, Humans, Mice, Models, Promoter Regions, Protein Binding, Transcription Factors},
	issn = {1088-9051},
	doi = {10.1002/cbic.201000254},
	author = {Chang, Li-Wei and Nagarajan, Rakesh and Magee, Jeffrey A and Milbrandt, Jeffrey and Stormo, Gary D}
}
