Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using ∼100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity. We found widespread correlated activity between enhancers, which decreases with increasing inter-...

Naive mouse embryonic stem cells (mESCs) and primed epiblast stem cells (mEpiSCs) represent successive snapshots of pluripotency during embryogenesis. Using transcriptomic and epigenomic mapping we show that a small fraction of transcripts are differentially expressed between mESCs and mEpiSCs and that these genes show expected changes in chromatin at their promoters and enhancers. Unexpectedly...

There have been numerous efforts to formulate insulin into an oral dosage form. The major problems involved with the oral administration of insulin are acidic and enzymatic decomposition by the gastric medium, and poor absorption in the small intestine due to its macromolecular structure. This study attempted to test the enhancing ability of two absorption enhancers, sodium glycocholate (Na-G...

Enhancers provide critical information directing cell-type-specific transcriptional programs, regulated by binding of signal-dependent transcription factors and their associated cofactors. Here, we report that the most strongly activated estrogen (E2)-responsive enhancers are characterized by trans-recruitment and in situ assembly of a large 1-2 MDa complex of diverse DNA-binding transcription ...

Morphological innovations such as the mammalian neocortex may involve the evolution of novel regulatory sequences. However, de novo birth of regulatory elements active during morphogenesis has not been extensively studied in mammals. Here, we use H3K27ac-defined regulatory elements active during human and mouse corticogenesis to identify enhancers that were likely active in the ancient mammalia...

there have been numerous efforts to formulate insulin into an oral dosage form. the major problems involved with the oral administration of insulin are acidic and enzymatic decomposition by the gastric medium, and poor absorption in the small intestine due to its macromolecular structure. this study attempted to test the enhancing ability of two absorption enhancers, sodium glycocholate (na-gc)...

Function and evolution of tele-enhancers ABSTRACT We investigated discriminating features between enhancers separated from their target genes by at least one intermediate gene/exon (named tele-enhancers in this study) and enhancers residing inside the target gene locus. In this study, we used genome-scale enhancer maps and whole-genome gene expression profiles to establish a large panel of hear...

Chromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrated analysis of islet data with those from nine cell types identified specific and significant enri...

Studies of regulatory activity and gene expression have revealed an intriguing dichotomy: There is substantial turnover in the regulatory activity of orthologous sequences between species; however, the expression level of orthologous genes is largely conserved. Understanding how distal regulatory elements, for example, enhancers, evolve and function is critical, as alterations in gene expressio...