Changes in chromatin organization during early development and carcinogenesis

Similar changes in chromatin organization take place during development and carcinogenesis. The size of chromatin loop domains fixed on the nuclear skeleton (matrix) increased from 20 to approximately 200 kbp. These changes are accompanied by an increased size of replicons and altered specificity of loop attachment to the nuclear matrix. During carcinogenesis, inverse changes in the chromatin structure are observed, neoplastic cells are dedifferentiated and return to the initial state. In this review, we consider new experimental data on organization of the DFNA loops and nuclear matrix in embryogenesis and carcinogenesis.     

Genome domains and domain regulatory elements

Gene activity regulation at the level of genome domains is considered with special emphasis on locus control regions (LCR), which are thought to act as dominant regulatory elements providing for the active state of tissue-specific gene domains. Detailed analysis was made of experimental data on the organization and function of mammalian beta-globin gene LCR. On recent evidence, this LCR is necessary for high-level expression of the globin genes, but not for the active state of the domain. These data are compared with earlier findings suggesting a key role of LCR in the organization of active genome domains. The boundaries of functional genome domains are also considered.     

Transgenic goats in the world's pharmaceutical industry in the XXI century

In many developed countries, isolation of human pharmaceutical proteins from milk of genetically modified animals is currently a priority. One of the first commercial pharmaceuticals obtained from the milk of transgenic goats, an anticoagulant antithrombin III, developed by Genzyme Transgenic Corporation, an American biotechnological company, will appear on the pharmaceutical market in the nearest future. In this review, we discuss the role of fundamental science in the development of this field of the pharmaceutical industry.     

The imprinting mechanism of the Prader-Willi/Angelman regional control center

The 2 Mb domain on chromosome 15q11-q13 that carries the imprinted genes involved in Prader-Willi (PWS) and Angelman (AS) syndromes is under the control of an imprinting center comprising two regulatory regions, the PWS-SRO located around the SNRPN promoter and the AS-SRO located 35 kb upstream. Here we describe the results of an analysis of the epigenetic features of these two sequences and their interaction. The AS-SRO is sensitive to DNase I, and packaged with acetylated histone H4 and methylated histone H3(K4) only on the maternal allele, and this imprinted epigenetic structure is maintained in dividing cells despite the absence of clearcut differential DNA methylation. Genetic analysis shows that the maternal AS-SRO is essential for setting up the DNA methylation state and closed chromatin structure of the neighboring PWS-SRO. In contrast, the PWS-SRO has no influence on the epigenetic features of the AS-SRO. These results suggest a stepwise, unidirectional program in which structural imprinting at the AS-SRO brings about allele-specific repression of the maternal PWS-SRO, thereby preventing regional activation of genes on this allele.     

Highlights of mycoplasma research—An historical perspective

This brief historical development of the biology of the mycoplasmas begins with their discovery in 1898 to the present. Mycoplasmas are the smallest free-living microorganisms and for years were thought to be viruses because they passed through the usual bacterial filters. They lack a cell wall, are widespread in nature and many are animal, plantand human pathogens. The extensive use of cell cultures in the last fifty years and their frequent contamination with mycoplasmas, together with their possession of the smallest genome of any free-living organism, has drawn enormous attention to these organisms and has revealed considerably more about their biology.     

Mechanism of heat stress-induced cellular senescence elucidates the exclusive vulnerability of early S-phase cells to mild genotoxic stress

Heat stress is one of the best-studied cellular stress factors; however, little is known about its delayed effects. Here, we demonstrate that heat stress induces p21-dependent cellular senescence-like cell cycle arrest. Notably, only early S-phase cells undergo such an arrest in response to heat stress. The encounter of DNA replication forks with topoisomerase I-generated single-stranded DNA breaks resulted in the generation of persistent double-stranded DNA breaks was found to be a primary cause of heat stress-induced cellular senescence in these cells. This investigation of heat stress-induced cellular senescence elucidates the mechanisms underlying the exclusive sensitivity of early S-phase cells to ultra-low doses of agents that induce single-stranded DNA breaks.