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Biomedical subjects

T I Lee

Publications and source records attributed to T I Lee.

11 recordsLinked to original sources
PubMed2001

Remodeling of yeast genome expression in response to environmental changes.

We used genome-wide expression analysis to explore how gene expression in Saccharomyces cerevisiae is remodeled in response to various changes in extracellular environment, including changes in temperature, oxidation, nutrients, pH, and osmolarity. The results demonstrate that more than half of the genome is involved in various responses to environmental change and identify the global set of genes induced and repressed by each condition. These data implicate a substantial number of previously uncharacterized genes in these responses and reveal a signature common to environmental responses that involves approximately 10% of yeast genes. The results of expression analysis with MSN2/MSN4 mutants support the model that the Msn2/Msn4 activators induce the common response to environmental change. These results provide a global description of the transcriptional response to environmental change and extend our understanding of the role of activators in effecting this response.

Adaptation, Physiological↗
PubMed2000

Redundant roles for the TFIID and SAGA complexes in global transcription.

The transcription factors TFIID and SAGA are multi-subunit complexes involved in transcription by RNA polymerase II. TFIID and SAGA contain common TATA-binding protein (TBP)-associated factor (TAF(II)) subunits and each complex contains a subunit with histone acetyltransferase activity. These observations have raised questions about whether the functions of the two complexes in vivo are unique or overlapping. Here we use genome-wide expression analysis to investigate how expression of the yeast genome depends on both shared and unique subunits of these two complexes. We find that expression of most genes requires one or more of the common TAF(II) subunits, indicating that the functions of TFIID and SAGA are widely required for gene expression. Among the subunits shared by TFIID and SAGA are three histone-like TAF(II)s, which have been proposed to form a sub-complex and mediate a common function in global transcription. Unexpectedly, we find that the histone-like TAF(II)s have distinct roles in expression of the yeast genome. Most importantly, we show that the histone acetylase components of TFIID and SAGA (TAF(II)145 and Gcn5) are functionally redundant, indicating that expression of a large fraction of yeast genes can be regulated through the action of either complex.

Acetyltransferases↗
PubMed2000

Transcription of eukaryotic protein-coding genes.

The past decade has seen an explosive increase in information about regulation of eukaryotic gene transcription, especially for protein-coding genes. The most striking advances in our knowledge of transcriptional regulation involve the chromatin template, the large complexes recruited by transcriptional activators that regulate chromatin structure and the transcription apparatus, the holoenzyme forms of RNA polymerase II involved in initiation and elongation, and the mechanisms that link mRNA processing with its synthesis. We describe here the major advances in these areas, with particular emphasis on the modular complexes associated with RNA polymerase II that are targeted by activators and other regulators of mRNA biosynthesis.

Chromatin↗
PubMed1998

Dissecting the regulatory circuitry of a eukaryotic genome.

Genome-wide expression analysis was used to identify genes whose expression depends on the functions of key components of the transcription initiation machinery in yeast. Components of the RNA polymerase II holoenzyme, the general transcription factor TFIID, and the SAGA chromatin modification complex were found to have roles in expression of distinct sets of genes. The results reveal an unanticipated level of regulation which is superimposed on that due to gene-specific transcription factors, a novel mechanism for coordinate regulation of specific sets of genes when cells encounter limiting nutrients, and evidence that the ultimate targets of signal transduction pathways can be identified within the initiation apparatus.

Acetyltransferases↗
PubMed1998

Interplay of positive and negative regulators in transcription initiation by RNA polymerase II holoenzyme.

Activation of protein-encoding genes involves recruitment of an RNA polymerase II holoenzyme to promoters. Since the Srb4 subunit of the holoenzyme is essential for expression of most class II genes and is a target of at least one transcriptional activator, we reasoned that suppressors of a temperature-sensitive mutation in Srb4 would identify other factors generally involved in regulation of gene expression. We report here that MED6 and SRB6, both of which encode essential components of the holoenzyme, are among the dominant suppressors and that the products of these genes interact physically with Srb4. The recessive suppressors include NCB1 (BUR6), NCB2, NOT1, NOT3, NOT5, and CAF1, which encode subunits of NC2 and the Not complex. NC2 and Not proteins are general negative regulators which interact with TATA box binding protein (TBP). Taken together, these results suggest that transcription initiation involves a dynamic balance between activation mediated by specific components of the holoenzyme and repression by multiple TBP-associated regulators.

Alleles↗
PubMed1997

Primary aldosteronism due to unilateral adrenal hyperplasia: a case report.

Primary aldosteronism is one of the differential diagnosis of secondary hypertension. This is usually caused by an aldosterone producing adenoma or bilateral adrenal hyperplasia which comprise about 65% and 30% of the cases, respectively. However, less than 1% of primary aldosteronism is caused by unilateral adrenal hyperplasia which is a relatively rare subset of primary aldosteronism. The clinical and biochemical manifestations of the disorder are indistinguishable from aldosterone-producing tumor, and a definitive diagnosis can only be made by pathological finding. A 33-year-old male Chinese patient presented with hypertension, hypokalemia, metabolic alkalosis, and the hypersecretion of aldosterone associated with suppressed plasma renin activity which is a typical hallmark of primary aldosteronism. Image studies including both magnetic resonance imaging (MRI) and 131I NIP-59 scan as well as postural test suggested an aldosterone-producing tumor of the right adrenal gland. Unilateral adrenectomy and pathological examination of the right adrenal gland eventually proved a case of unilateral adrenal hyperplasia. Blood pressure, plasma potassium, aldosterone and renin activity levels returned to normal two weeks after operation and had remained normal at up to one year of follow up. In addition, a saline loading test showed normal suppression of plasma aldosterone level one year after the operation, suggesting that the function of the left adrenal gland remains normal. The etiology of unilateral adrenal hyperplasia is unclear and the future recurrence of the disease is possible. Long-term follow-up is necessary to ensure the cure of this disorder.

Adrenal Glands↗
PubMed1977

Adverse reactions to drugs: a 12-month hospital survey.

A formalised system of adverse drug reaction (ADR) reporting was instituted at the Royal Adelaide Hospital in August 1975. The present report reviews the results obtained from this system after a 12-month period of operation. A significant number of reports associated with the use of antibiotics and radiographic contrast media were received. The importance of "feed-back" of ADR information to prescribers is emphasised.

Anti-Bacterial Agents↗
PubMed1975

Extensive drug surveillance--a pilot study.

The aim of this Extensive Drug Surveillance programme was to develop a system of drug monitoring suitable for detecting adverse drug reactions in hospitalised patients. The monitored field was a general medical ward in the Royal Adelaide Hospital and monitoring was carried out for a period of one month (September 1974). A total of 85 patients (45 males and 40 females) were monitored and in 14 of them adverse reactions were noted. The overall incidence of such reactions was 16.5%. A greater intake of drugs was a significant finding in patients who experienced adverse reactions. Coupled with this was the observation that patients who stayed longer in hospital had a greater number of drugs administered to them. A third finding was the higher incidence of reactions in female patients.

Drug Prescriptions↗