Global reference mapping of human transcription factor footprints.

Combinatorial binding of transcription factors to regulatory DNA underpins gene regulation in all organisms. Genetic variation in regulatory regions has been connected with diseases and diverse phenotypic traits, but it remains challenging to distinguish variants that affect regulatory function. Genomic DNase I footprinting enables the quantitative, nucleotide-resolution delineation of sites of transcription factor occupancy within native chromatin.

Index and biological spectrum of human DNase I hypersensitive sites.

DNase I hypersensitive sites (DHSs) are generic markers of regulatory DNA and contain genetic variations associated with diseases and phenotypic traits. We created high-resolution maps of DHSs from 733 human biosamples encompassing 438 cell and tissue types and states, and integrated these to delineate and numerically index approximately 3.6 million DHSs within the human genome sequence, providing a common coordinate system for regulatory DNA.

Mesh versus non-mesh for inguinal and femoral hernia repair.

Background: This is an update of a Cochrane Review first published in 2001.Hernias are protrusions of all or part of an organ through the body wall that normally contains it. Groin hernias include inguinal (96%) and femoral (4%) hernias, and are often symptomatic with discomfort.

Mitral valve surgery and coronary artery bypass grafting for moderate-to-severe ischemic mitral regurgitation: Meta-analysis of clinical and echocardiographic outcomes.

Objective: This meta-analysis was conducted to compare clinical and echocardiographic outcomes following isolated coronary artery bypass grafting (CABG) versus CABG and mitral valve (MV) surgery in patients with moderate-to-severe ischemic mitral regurgitation (IMR).

Methods: Seven databases were systematically searched to identify relevant studies. For eligibility, studies were required to report on the primary endpoint of perioperative or late mortality.

A systematic review and meta-analysis of multidetector computed tomography in the assessment of coronary artery bypass grafts.

Purpose: The present meta-analysis aimed to compare the diagnostic accuracy of more recent computed tomography coronary angiography (CTCA) with invasive coronary angiography (ICA) in the assessment of graft patency after coronary artery bypass graft surgery (CABG).

Material And Methods: A systematic review was performed using nine electronic databases from their dates of inception to July 2015. Predefined inclusion criteria included studies reporting on comparative outcomes using ≥64 slice multidetector computed tomography (MDCT) and ICA.

A meta-analysis of mitral valve repair versus replacement for ischemic mitral regurgitation.

Background: The development of ischemic mitral regurgitation (IMR) portends a poor prognosis and is associated with adverse long-term outcomes. Although both mitral valve repair (MVr) and mitral valve replacement (MVR) have been performed in the surgical management of IMR, there remains uncertainty regarding the optimal approach. The aim of the present study was to meta-analyze these two procedures, with mortality as the primary endpoint.

Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution.

To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements.

Conservation of trans-acting circuitry during mammalian regulatory evolution.

The basic body plan and major physiological axes have been highly conserved during mammalian evolution, yet only a small fraction of the human genome sequence appears to be subject to evolutionary constraint. To quantify cis- versus trans-acting contributions to mammalian regulatory evolution, we performed genomic DNase I footprinting of the mouse genome across 25 cell and tissue types, collectively defining ∼8.6 million transcription factor (TF) occupancy sites at nucleotide resolution.

A comparative encyclopedia of DNA elements in the mouse genome.

The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.

An expansive human regulatory lexicon encoded in transcription factor footprints.

Regulatory factor binding to genomic DNA protects the underlying sequence from cleavage by DNase I, leaving nucleotide-resolution footprints. Using genomic DNase I footprinting across 41 diverse cell and tissue types, we detected 45 million transcription factor occupancy events within regulatory regions, representing differential binding to 8.4 million distinct short sequence elements.

The accessible chromatin landscape of the human genome.

DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ∼2.