Endocrine Abstracts

Dr Hager received his PhD in Genetics at the University of Washington, and pursued postdoctoral studies with Dick Epstein at the Institut de Biologie Moleculaire in Geneva and with Dr William Rutter at the University of California-San Francisco. After moving to the NIH, he developed the mouse mammary tumor virus (MMTV) system as a model to study hormonal regulation of gene expression, and utilized this system to descr...

In response to hormone activation of the glucocorticoid receptor, GR responsive promoters move through a complex series of activity states, a phenomenon we term promoter progression. Genome-wide profiling of glucocorticoid receptor (GR) regulated loci reveals several classes of response, including genes that are transiently activated and genes that are transiently repressed. In contrast to the conventional paradigm of activation and repression, GR modulation of genome function...

The peroxisome proliferator-activated receptors (PPARs) display a high degree of conservation in the DNA- and ligand-binding domains. Despite these sequence similarities, the PPARs show distinct functions, even when co-expressed. Many experimental approaches have been employed to determine the molecular mechanisms that underlie their subtype-specific characteristics. However, these approaches have largely relied on cell population based studies, such as ChIP-seq. Here we have ...

Ultradian glucocorticoid (GC) secretion is highly conserved, having been detected in all species studied. The GC corticosterone (CORT) is a ligand for the glucocorticoid receptor (GR), inducing GR recruitment to glucocorticoid responsive elements (GREs) to modulate transcription of GC-target genes. We have previously demonstrated that pulsatile GR recruitment to GREs upstream of the Period1 gene is associated with its pulsatile transcription in rat liver. Similarly th...

Transcription factors (TFs) regulate gene expression by interacting with chromatinized DNA response elements (REs). Access to these elements is dramatically restricted by chromatin organization, and modification of the nucleoprotein structure to allow factor binding is a key feature of cell selective gene regulation (Molecular Cell 29:611, 2008; Molecular Cell 43:145, 2011). Local transitions in chromatin access (often characterized as DNaseI hypersensitive sites (DHSs)) are o...

Glucocorticoid actions in the brain are mediated by glucocorticoid receptors (GR) and mineralocorticoid receptors (MR). MR and GR bind endogenously circulating glucocorticoids, share a hormone response element in DNA, and are co-expressed in neurons of the hippocampus and hypothalamus. This arrangement suggests MR and GR functionally cooperate in the regulation of gene expression though hitherto poorly described mechanisms. This possibility was previously exampled by the demon...

Glucocorticoids act via the glucocorticoid receptor (GR). Upon ligand binding, GR translocates to the nucleus and binds directly to glucocorticoid responsive elements (GREs) to regulate transcriptional output. Glucocorticoid secretion increases in response to stress to affect transcriptional output within specific areas of the brain including the hippocampus (HC). Therefore, here we assess changes in genome-wide GR chromatin binding profiles in the rat HC in response to a gluc...