- Estrogen and related hormone effects
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Pancreatic function and diabetes
- Animal Genetics and Reproduction
- Reproductive System and Pregnancy
- RNA and protein synthesis mechanisms
- Nuclear Receptors and Signaling
- Hormonal Regulation and Hypertension
- Genetics and Neurodevelopmental Disorders
- Prostate Cancer Treatment and Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Retinoids in leukemia and cellular processes
- Mobile Ad Hoc Networks
- Energy Efficient Wireless Sensor Networks
- Steroid Chemistry and Biochemistry
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Cell Adhesion Molecules Research
- Congenital heart defects research
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Angiogenesis and VEGF in Cancer
National Tsing Hua University
2013-2024
Baylor College of Medicine
2012-2023
National Taiwan University
2002-2022
Kaohsiung Medical University
2018
Kaohsiung Medical University Chung-Ho Memorial Hospital
2018
National Institute of Environmental Health Sciences
2016
National Yang Ming Chiao Tung University
2012
Institut de Biologie Moléculaire et Cellulaire
2008
University of California, San Francisco
2000-2006
Karolinska Institutet
1997-2006
A yeast two-hybrid system was used to identify a protein that interacts with and enhances the human progesterone receptor (hPR) transcriptional activity without altering basal of promoter. Because stimulated transactivation all steroid receptors tested, it has been termed coactivator-1 (SRC-1). Coexpression SRC-1 reversed ability estrogen squelch activation by hPR. Also, amino terminal truncated form acted as dominant-negative repressor. Together, these results indicate encodes coactivator...
Candidate transcription factors involved in pancreatic endocrine development have been isolated using insulin gene regulation as a paradigm. The cell-type restricted basic helix–loop–helix (bHLH) gene, BETA2/NeuroD, expressed cells, the intestine, and brain, activates can induce neurons to differentiate. To understand importance of BETA2 cell differentiation, mice lacking functional were generated by targeting experiments. Mice carrying targeted disruption developed severe diabetes died...
The in vivo biological function of a steroid receptor coactivator was assessed mice which the SRC-1 gene inactivated by targeting. Although both sexes homozygous mutants were viable and fertile, target organs such as uterus, prostate, testis, mammary gland exhibited decreased growth development response to hormones. Expression RNA encoding TIF2, member family, increased null mutant, perhaps compensating partially for loss tissues. results indicate that mediates hormone responses its partial...
BETA2/NeuroD1 is a bHLH transcription factor that expressed during development in the mammalian pancreas and many locations central peripheral nervous systems. During inner ear ontogenesis, it present both sensory ganglion neurons epithelia. Although studies have shown important of hippocampal dentate gyrus cerebellum, its functions system particular are unclear. Mice carrying null mutation exhibit behavioral abnormalities suggestive an defect, including lack responsiveness to sound,...
The insulin gene is one of the best paradigms tissue-specific expression. It developmentally regulated and expressed exclusively in pancreatic beta-cell. This restricted expression directed by a enhancer, within promoter, which contains an E-box sequence. binds islet-specific protein complex, termed 3a1. E-boxes bind proteins belonging to basic helix-loop-helix (bHLH) family transcription factors. bHLH function as potent transcriptional activators genes forming heterodimers between...
The origin of the mammalian lymphatic vasculature has been debated for more than 100 years. Whether endothelial cells have a single or dual, venous mesenchymal remains controversial. To resolve this debate, we performed Cre/loxP -based lineage-tracing studies using mouse strains expressing Cre recombinase under control Tie2 , Runx1 Prox1 promoter elements. These studies, together with analysis -mutant embryos lacking definitive hematopoiesis, conclusively determined that from venous-derived...
The embryonic expression of COUP-TFII, an orphan nuclear receptor, suggests that it may participate in mesenchymal-epithelial interactions required for organogenesis. Targeted deletion the COUP-TFII gene results lethality with defects angiogenesis and heart development. mutants are defective remodeling primitive capillary plexus into large small microcapillaries. In mutant heart, atria sinus venosus fail to develop past tube stage. Reciprocal between endothelium mesenchyme vascular system...
In diabetes, the death of insulin-producing β-cells by apoptosis leads to insulin deficiency. The lower prevalence diabetes in females suggests that female sex steroids protect from β-cell injury. Consistent with this hypothesis, 17β-estradiol (estradiol) manifests antidiabetic actions humans and rodents. addition, estradiol has antiapoptotic cells are mediated estrogen receptor-a (ERα), raising prospect function may be due, part, a protection via ERα. To address question, we have used mice...
In this study, we found that the E6-associated protein (E6-AP/UBE3A) directly interacts with and coactivates transcriptional activity of human progesterone receptor (PR) in a hormone-dependent manner. E6-AP also activities other members nuclear hormone superfamily. Previously, it was shown serves role ubiquitin-protein ligase (E3) presence E6 from papillomavirus types 16 18. Our data show function is dispensable for its ability to coactivate receptors, showing possesses two separable...
Steroid receptors are ligand-inducible transcription factors, and their association with steroid receptor coactivators (SRCs) upon binding to DNA is necessary for them achieve full transcriptional potential. To understand the mechanism of SRC-1 action, its ability interact enhance activity was analyzed. First, we show that a modular coactivator possesses intrinsic when tethered it harbors two distinct activation domains, AD1 AD2, needed maximum coactivation function receptors. We also...
Steroid receptors are ligand-regulated transcription factors that require coactivators for efficient activation of target gene expression. The binding protein cAMP response element (CBP) appears to be a promiscuous coactivator an increasing number and the ability CBP modulate estrogen receptor (ER)- progesterone (PR)-dependent was therefore examined. Ectopic expression or related coactivator, p300, enhanced ER transcriptional activity by up 10-fold in receptor- DNA-dependent manner....
Alignment of natural chicken ovalbumin upstream promoter transcription factor (COUP-TF) response elements shows that, in addition to the predominant direct repeat GGTCA motif with a 2-bp spacing, there are other functional COUP variations orientation and spacing. We systematically analyzed binding vitro-synthesized COUP-TFs showed that COUP-TF is capable oligonucleotides containing both repeats palindromes different spacings repeats. Subsequently, we four possible mechanisms proposed explain...
Antihormones are potent antagonists of hormone action in vivo, but the mechanism underlying this antagonism is not understood. Several steroid hormones transform (activate) their receptors from a cytosolic, non-DNA binding 8 S sedimentation form to nuclear, DNA 4 form. Transformation accompanied by loss associated heat shock proteins. We have previously demonstrated that an additional hormone-dependent step, separate protein removal, required for activation human progesterone receptor....
Neurogenin-3 (NEUROG3) is expressed in endocrine progenitor cells and required for endocrine-cell development the pancreas intestine. The NEUROG3 gene therefore a candidate cause of newly discovered autosomal recessive disorder characterized by generalized malabsorption paucity enteroendocrine cells.We screened genomic DNA from three unrelated patients with sparse mutations NEUROG3. We then tested ability observed to alter function, using vitro vivo assays.The had few intestinal positive...