Nucleolar chromatin

Abstract: The presence of extrachromosomal nucleoli in amphibian oocytes has permitted isolation and electron microscopic observation of the genes coding for ribosomal RNA precursor molecules. Visualization of these genes is possible because many precursor molecules are simultaneously synthesized on each gene. Individual genes are separated by stretches of DNA that apparently are not transcribed at the time of synthesis of precursor rRNA in the extrachromosomal nucleoli.

Abstract: Cells require optimum protein synthetic activity in order to support cell proliferation, maintain homeostatic and metabolic integrity, and repair damage. Since growth depends on protein synthesis through ribosome biogenesis, the control of biosynthesis of ribosomes is necessarily a key element for control of growth. Nucleolin is a major nucleolar protein of exponentially growing eukaryotic cells, which is directly involved in the regulation of ribosome biogenesis and maturation. The highly conserved nucleolin contains three major domains through which it controls the organization of nucleolar chromatin, packaging of pre-RNA, rDNA transcription, and ribosome assembly. Numerous reports have implicated the involvement of nucleolin either directly or indirectly in the regulation of cell proliferation and growth, cytokinesis, replication, embryogenesis, and nucleogenesis. Nucleolin, an RNA binding protein, is also an autoantigen, a transcriptional repressor, and a switch region targeting factor. In addition, n...

Abstract: Publisher Summary The nucleolus is organized at the nucleolus-organizing region of the chromosomes, which are generally visible as secondary constriction regions in metaphase chromosomes. The chromatin within the constriction region is lost at interphase inside the nucleolar mass. The chromatin is highly extended at this stage. At the ultrastructural level, the nucleolus has at least three components: (1) a granular component consisting mainly of ribonucleoproteins (RNP) granules—pars granulosa, (2) a fibrillar component, consisting of RNP fibrils—pars fibrosa, and (3) chromatin elements. Chromatin elements may be present in three forms: (1) nucleolus-associated chromatin, which most likely does not take part in nucleolus formation; however, the possibility of its association with condensed inactive ribosomal cistrons, at least in some cells, cannot be overruled at present, (2) septalike intranucleolar chromatin, and (3) isolated or dispersed intranucleolar chromatin threads. Intranucleolar chromatin is often associated with the pars fibrosa. Identical components can also be found in isolated nucleoli. Studies on the nucleoli in giant chromosomes indicate that the intranucleolar chromatin in these nucleoli is present as puffs of different sizes. The nucleolar chromatin is not an autonomous structure of the nucleolus but is a continuous structure and part of the nucleolar chromosome.

Abstract: Transcription by RNA polymerase I on nucleosomal templates requires binding of the transcription termination factor TTF-I to a cognate site 160 bp upstream of the transcription start site. Binding of TTF-I is accompanied by changes in the chromatin architecture which suggests that TTF-I recruits a remodeling activity to the rDNA promoter. We have cloned a cDNA that encodes TIP5 (TTF-I-interacting protein 5), a 205 kDa protein that shares a number of important protein domains with WSTF (Williams syndrome transcription factor) and hAcf1/WCRF180, the largest subunits of human chromatin remodeling complexes hCHRAC and WCRF. TIP5 co-localizes with the basal RNA polymerase I transcription factor UBF in the nucleolus and is associated with SNF2h. The cellular TIP5–SNF2h complex, termed NoRC (nucleolar remodeling complex), induces nucleosome sliding in an ATP- and histone H4 tail-dependent fashion. The results suggest that NoRC is a novel nucleolar chromatin remodeling machine that may serve a role in the regulation of the rDNA locus.

Abstract: The existing literature on studies of the inhibitory effect of moderate heat doses on malignant tumours is briefly reviewed. An experimental technique of heat treatment of mouse tumours in vivo under accurate control of the intratumoural temperature is described. In experiments with an isologous transplantable mouse mammary carcinoma, controlled application of a moderate heat dose led, in many cases, to a permanent cure of the transplanted tumour without causing any damage to the surrounding normal tissue. The necessary heat doses in the temperature range of 41·5 to 43·5°C are worked out revealing a definite relationship between temperature and exposure time. The heat treatment induces distinct histological changes in the tumour cells, whereas it does not cause any damage to the stromal and vascular cells in the tumour, or to the surrounding normal tissue. Immediately after the heat application, definite changes were revealed in the mitochondria and lysosomes of the tumour cells. These changes increased in intensity with the size of the heat dose and become more pronounced within a few hours or days. Within the first few hours, changes in the nuclei of the tumour cells and in chromosomal and nucleolar chromatin developed, with some variation in the individual cells. 24 hr after the application of a curative dose, all tumour cells showed severe injury. After smaller doses the reaction to the heat was less intense, with variations in the individual cells, and several tumour cells did not show any signs of lethal injury. Autolytic disintegration of the heat-damaged tumour cells occurs very rapidly. The connective tissue of the stroma increases markedly in volume, and a scar forms. The histological examination did not reveal all details of the process, but in the light of biochemical observations, it is reasonable to assume that the direct effect of heat is due to an elective activation of the acid hydrolases localized in the lysosomes of the tumour cells.