Transcription factors (TFs) exert their regulatory influence through the binding of enhancers, resulting in coordination of gene expression programs. Active enhancers are often characterized by the presence of short, unstable transcripts termed enhancer RNAs (eRNAs). While their function remains unclear, we demonstrate that eRNAs are a powerful readout of TF activity.
View Article and Find Full Text PDFHistone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal and cancer cells. However, the exact regulatory mechanisms of action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic and transcriptome changes in response to HDACI largazole in a transformed and a non-transformed cell line.
View Article and Find Full Text PDFMotivation: Transcription by RNA polymerase is a highly dynamic process involving multiple distinct points of regulation. Nascent transcription assays are a relatively new set of high throughput techniques that measure the location of actively engaged RNA polymerase genome wide. Hence, nascent transcription is a rich source of information on the regulation of RNA polymerase activity.
View Article and Find Full Text PDFA mixture model and statistical method is proposed to interpret the distribution of reads from a nascent transcriptional assay, such as global run-on sequencing (GRO-seq) data. The model is annotation agnostic and leverages on current understanding of the behavior of RNA polymerase II. Briefly, it assumes that polymerase loads at key positions (transcription start sites) within the genome.
View Article and Find Full Text PDFIEEE/ACM Trans Comput Biol Bioinform
May 2018
We present a fast and simple algorithm to detect nascent RNA transcription in global nuclear run-on sequencing (GRO-seq). GRO-seq is a relatively new protocol that captures nascent transcripts from actively engaged polymerase, providing a direct read-out on bona fide transcription. Most traditional assays, such as RNA-seq, measure steady state RNA levels which are affected by transcription, post-transcriptional processing, and RNA stability.
View Article and Find Full Text PDFStudying the importance of genetic factors in a desired cell type or tissue necessitates the use of precise genetic tools. With the introduction of bacteriophage Cre recombinase/loxP mediated DNA editing and promoter-specific Cre expression, it is feasible to generate conditional knockout mice in which particular genes are disrupted in a cell type-specific manner in vivo. In cardiac myocytes, this is often achieved through α-myosin heavy chain promoter (αMyHC)-driven Cre expression in conjunction with a loxP-site flanked gene of interest.
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