Project description:Heat stress represents a major constraint to cattle productivity in tropical environments, with breed-specific differences in thyroid hormone metabolism potentially underlying variation in thermal resilience. This study investigated expression of selected candidate genes related to thyroid metabolism, mitochondrial function, lipid metabolism, growth signaling, and stress response across three cattle genotypes to explore the underlying roles of thyroid hormone metabolism in heat adaptation. Whole blood RNA-seq was performed on samples from heat-tolerant Kedah-Kelantan (KK), intermediate Brangus (BR), and heat-vulnerable Holstein Friesian (HF) cattle during peak heat load (Temperature-Humidity Index: 44.68). Of 20 genes analyzed, 17 showed significant differential regulation across the breeds. These findings demonstrate that breed-specific heat resilience is associated with coordinated regulation of deiodinase pathways and integrated lipid-mitochondrial-stress networks
Project description:Using tadpoles mutant for thyroid hormone receptor alpha (thra), we show that TRa is required for thyroid hormone (T3) induction of cell proliferation in the brain. RNA-sequencing showed that the TRa is required for 95% of the gene regulation responses to T3.
Project description:Metabolomics dataset of serum from T3-treated dams. Related to following publication by Oelkrug et al: "Maternal thyroid hormone receptor beta activation sparks brown fat thermogenesis in the offspring"
Project description:The goal of our present work was to understand the influence parvovirus B19 infection may have on the thyroid hormone signaling pathway, as well as the nuclear receptors (NR) pathway overall. We demonstrated that B19 infection of CD36+ erythroid progenitor cells leads to downregulation of the thyroid hormone receptor α isoform. In addition to that we have shown that B19 infection modulates the expression of other members of the NR superfamily such as estrogen and retinoid receptors.
Project description:The ligand-bound vitamin D receptor (VDR) recruits the E3 ligase FBW7 to enhance the proteasomal turnover of the DNA-bound transcription factor cMYC (2, 3). Unexpectedly, FBW7 functions as a cofactor of VDR trans-activation and is recruited to VDR target genes. Our goals are to understand the role of the E3 ligase FBW7 as a cofactor of transcriptional regulation using engineered cell lines responsive to multiple nuclear receptor ligands. In addition to its effects on VDR signaling, we recently found that ablation of FBW7 strongly compromises transactivation by related retinoic acid receptors (RARs) and by estrogen receptor alpha (ER alpha). We will extend these findings to analyze global effects of FBW7 ablation on hormone-regulated gene transcription and the ligand-dependent (and –independent), genome-wide recruitment of FBW7 to chromatin. These studies will establish the extent and mechanisms of action of FBW7 as a regulator of nuclear receptor- and non-nuclear receptor-regulated gene transcription.
Project description:Thyroid hormones are important for homeostatic control of energy metabolism and body temperature. Although skeletal muscle is considered an important site for thyroid action, the contribution of thyroid hormone receptor signaling, in muscle, to whole-body energy metabolism and body temperature has not been resolved. Here, we show that thyroid hormone-induced increase in energy expenditure requires thyroid hormone receptor alpha 1 (TRa1) in skeletal muscle, but that thyroid hormone induced elevation in body temperature is independent of muscle-TRa1. In slow-twitch soleus muscle, ablation of TRa1 leads to an altered fiber type composition toward a more oxidative phenotype, which, however, does not influence running capacity or motivation to voluntary running. RNA-sequencing of soleus muscle from WT mice and TRaHSACre mice revealed differentiated transcriptional regulation of genes associated with muscle thermogenesis, such as sarcolipin and UCP3, thus providing molecular clues pertaining to the mechanistic underpinnings of TRa1-linked control of whole-body metabolic rate. Together, this work establishes a fundamental role for skeletal muscle in thyroid hormone-stimulated increase in whole-body energy expenditure.
Project description:This SuperSeries is composed of the following subset Series: GSE32443: Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1 [Affymetrix] GSE32444: Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1 [Illumina] Refer to individual Series
