Louise Hunter

The University of Manchester · School of Medical Sciences

The nuclear receptor REVERBα is a core component of the circadian clock and proposed to be a dominant regulator of hepatic lipid metabolism. Using antibody-independent ChIP-sequencing of REVERBα in mouse liver, we reveal a high-confidence cistrome and define direct target genes. REVERBα-binding sites are highly enriched for consensus RORE or RevDR2...

Many biological studies of transcriptional control mechanisms produce lists of genes and non-coding genomic intervals from corresponding gene expression and epigenomic assays. In higher organisms, such as eukaryotes, genes may be regulated by distal elements, with these elements lying 10s–100s of kilobases away from a gene transcription start site....

The circadian clock component NR1D1 (REVERBα) is considered a dominant regulator of lipid metabolism, with global Nr1d1 deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion ( Nr1d1 Flox2-6 :Adipoq Cre ), and transcriptional pro1ling demo...

The glucocorticoid receptor (GR) is a nuclear receptor critical to the regulation of energy metabolism and inflammation. The actions of GR are dependent on cell type and context. Here, we demonstrate the role of liver lineage-determining factor hepatocyte nuclear factor 4A (HNF4A) in defining liver specificity of GR action. In mouse liver, the HNF4...

Chromatin immunoprecipitation (ChIP) maps, on a genome-wide scale, transcription factor binding sites, and the distribution of other chromatin-associated proteins and their modifications. As such, it provides valuable insights into mechanisms of gene regulation. However, successful ChIP experiments are dependent on the availability of a high-qualit...

The circadian clock controls the physiological function of tissues through the regulation of thousands of genes in a cell‐type‐specific manner. The core cellular circadian clock is a transcription–translation negative feedback loop, which can recruit epigenetic regulators to facilitate temporal control of gene expression. Histone methyltransferase,...

Many biological studies of transcriptional control mechanisms produce lists of genes and non-coding genomic intervals from corresponding gene expression and epigenomic assays. In higher organisms, such as eukaryotes, genes may be regulated by distal elements, with these elements lying 10s–100s of kilobases away from a gene transcription start site....

The glucocorticoid receptor (GR) is a nuclear hormone receptor critical to the regulation of energy metabolism and the inflammatory response. The actions of GR are highly dependent on cell type and environmental context. Here, we demonstrate the necessity for liver lineage-determining factor hepatocyte nuclear factor 4A (HNF4A) in defining liver-sp...

The circadian clock component REVERBα is considered a dominant regulator of lipid metabolism, with global Reverbα deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion ( Reverbα Flox2-6 Adipo Cre ), and transcriptional profiling demonstra...

The liver is a critical organ of energy metabolism. At least 10% of the liver transcriptome demonstrates rhythmic expression, implying that the circadian clock regulates large programmes of hepatic genes. Here, we review the mechanisms by which this rhythmic regulation is conferred, with a particular focus on the transcription factors whose actions...

Chromatin immunoprecipitation (ChIP) is a valuable tool for the endocrine researcher, providing a means to measure the recruitment of hormone-activated nuclear receptors, for example. However, the technique can be challenging to perform and has multiple experimental steps, risking introduction of error at each. The data produced can be challenging...

Pulmonary airway epithelial cells (AECs) form a critical interface between host and environment. We investigated the role of the circadian clock using mice bearing targeted deletion of the circadian gene brain and muscle ARNT-like 1 ( Bmal1) in AECs. Pulmonary neutrophil infiltration, biomechanical function, and responses to influenza infection wer...

The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis — all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained...

Background: TSH receptor antibody (TRAb) is considered the gold standard diagnostic test for the autoimmunity of Graves' disease (GD), which is commonly diagnosed clinically. Aim: To evaluate the true positive (sensitivity) and true negative (specificity) rates of clinical diagnosis of GD or non-GD hyperthyroidism compared to the TRAb test. Setting...

Supplementary material

Supplementary material

Supplementary material

Supplementary material

Supplementary material

Objectives: The aim of this systematic literature review was to summarize the current knowledge regarding the prevalence of, time to recovery from, and influence of glucocorticoid dose and duration on glucocorticoid-induced adrenal insufficiency (AI). Methods: Eligible studies were original research articles, which included adult patients with a...

We present two patients with significant hypokalaemia initially attributed to liquorice use. Case 1: A 52-year-old engineer was noted to have a potassium level of 2.5 mmol/l (3.5–5.3 mmol/l) at a Well Man check-up. He had no significant past history, and took no medications. He was normotensive. The patient reported regular liquorice use. The hypok...

Introduction: The prevalence of clinical obesity in women with polycystic ovarian syndrome (PCOS) is 50%. Weight loss is effective at enhancing insulin sensitivity, reducing hyperandrogenaemia, improving hirsutism and restoring menstrual regularity and fertility in PCOS. However, women with PCOS appear to be less responsive to weight loss intervent...

The Quality and Outcomes Framework for diabetes mellitus has led to an improvement in diabetes management since its introduction in 2004. However, the focus on reduction of HbA1c must not detract from a holistic approach to patient care. We present the case of a patient whose unexpected decline in HbA1c levels culminated in an emergency presentatio...

Pathological stress responses are implicated in numerous disorders. Hypothalamic-pituitary-adrenal axis function is influenced by gene-environment interaction, with early-life environmental adversity having long-lasting effects. We examine the evidence that, in humans, these effects are apparent from infancy. We systematically reviewed published fi...