ABSTRACT
Alterations in the rate of cell proliferation are accompanied by changes in the transcription of rRNA genes. In mammals, this growth-dependent regulation of transcription of genes coding for rRNA (rDNA) is due to reduction of the amount or activity of an essential transcription factor, called TIF-IA. Extracts prepared from quiescent cells lack this factor activity and, therefore, are transcriptionally inactive. We have purified TIF-IA from exponentially growing cells and have shown that it is a polypeptide with a molecular mass of 75 kDa which exists as a monomer in solution. Using a reconstituted transcription system consisting of purified transcription factors, we demonstrate that TIF-IA is a bona fide transcription initiation factor which interacts with RNA polymerase I. Preinitiation complexes can be assembled in the absence of TIF-IA, but formation of the first phosphodiester bonds of nascent rRNA is precluded. After initiation, TIF-IA is liberated from the initiation complex and facilitates transcription from templates bearing preinitiation complexes which lack TIF-IA. Despite the pronounced species specificity of class I gene transcription, this growth-dependent factor has been identified not only in mouse but also in human cells. Murine TIF-IA complements extracts from both growth-inhibited mouse and human cells. The analogous human activity appears to be similar or identical to that of TIF-IA. Therefore, despite the fact that the RNA polymerase transcription system has evolved sufficiently rapidly that an rDNA promoter from one species will not function in another species, the basic mechanisms that adapt ribosome synthesis to cell proliferation have been conserved.
Subject(s)
DNA, Ribosomal/metabolism , Gene Expression Regulation, Neoplastic , Promoter Regions, Genetic , RNA, Ribosomal/genetics , Transcription Factors/metabolism , Transcription, Genetic , Animals , Carcinoma, Ehrlich Tumor , Cell Division , Cell Nucleus/metabolism , Chromatography, Gel , Cytoplasm/metabolism , Electrophoresis, Polyacrylamide Gel , Genes, MHC Class I , HeLa Cells , Humans , Kinetics , Mice , Templates, Genetic , Transcription Factors/isolation & purification , Tumor Cells, CulturedABSTRACT
We report a case of intraocular mycosis fungoides in a 48-year-old man. The patient presented with decreased visual acuity, white subretinal lesions, and vitritis. Post-mortem histopathology revealed malignant T cell infiltrates consistent with mycosis fungoides in the retina, vitreous, and between the retinal pigment epithelium (RPE) and Bruch's membrane Focal atrophy of the RPE, along with the sub-RPE infiltrates, correlated with the clinically visible fundus lesions.
Subject(s)
Eye Neoplasms/secondary , Mycosis Fungoides/pathology , Pigment Epithelium of Eye , Skin Neoplasms/pathology , Bruch Membrane/pathology , Eye Neoplasms/pathology , Fundus Oculi , Humans , Male , Middle Aged , Pigment Epithelium of Eye/pathology , Retina/pathology , Vitreous Body/pathologyABSTRACT
The study of the circadian sleep-wake cycle is beset by unique technical challenges. Continuous polygraphic recordings are necessary to characterize circadian phenomena; however, the traditional method of recording sleep at high (15 mm/sec) chart speed is impractical for continuous animal studies that may last several weeks at a stretch. A system to determine four sleep-wake stages (awake, transitional, non-REM, REM) from low chart speed (1.5 mm/sec) recordings was developed and validated by direct behavioral observation using four adult male squirrel monkeys prepared for chronic recording of EEG, EOG and EMG. The polygraphic stages "transitional," non-REM and REM were highly correlated with behavioral observations of sleep, although individual sleep stages could not be resolved by behavioral parameters alone.
