Nejvíce citovaný článek - PubMed ID 8947544
The study of embryonic stem cells is in the spotlight in many laboratories that study the structure and function of chromatin and epigenetic processes. The key properties of embryonic stem cells are their capacity for self-renewal and their pluripotency. Pluripotent stem cells are able to differentiate into the cells of all three germ layers, and because of this property they represent a promising therapeutic tool in the treatment of diseases such as Parkinson's disease and diabetes, or in the healing of lesions after heart attack. As the basic nuclear unit, chromatin is responsible for the regulation of the functional status of cells, including pluripotency and differentiation. Therefore, in this review we discuss the functional changes in chromatin during differentiation and the correlation between epigenetics events and the differentiation potential of embryonic stem cells. In particular we focus on post-translational histone modification, DNA methylation and the heterochromatin protein HP1 and its unique function in mouse and human embryonic stem cells.
- Klíčová slova
- Chromatin, Differentiation, Embryonic stem cells, Epigenetics, Nucleus, Pluripotency,
- Publikační typ
- časopisecké články MeSH
The nucleolus is a nuclear compartment that plays an important role in ribosome biogenesis. Some structural features and epigenetic patterns are shared between nucleolar and non-nucleolar compartments. For example, the location of transcriptionally active mRNA on extended chromatin loop species is similar to that observed for transcriptionally active ribosomal DNA (rDNA) genes on so-called Christmas tree branches. Similarly, nucleolus organizer region-bearing chromosomes located a distance from the nucleolus extend chromatin fibers into the nucleolar compartment. Specific epigenetic events, such as histone acetylation and methylation and DNA methylation, also regulate transcription of both rRNA- and mRNA-encoding loci. Here, we review the epigenetic mechanisms and structural features that regulate transcription of ribosomal and mRNA genes. We focus on similarities in epigenetic and structural regulation of chromatin in nucleoli and the surrounding non-nucleolar region and discuss the role of proteins, such as heterochromatin protein 1, fibrillarin, nucleolin, and upstream binding factor, in rRNA synthesis and processing.
- MeSH
- buněčné jadérko genetika metabolismus ultrastruktura MeSH
- chromatin genetika ultrastruktura MeSH
- epigeneze genetická * MeSH
- genetická transkripce MeSH
- geny rRNA MeSH
- histony metabolismus MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- ribozomální DNA genetika MeSH
- ribozomy genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- srovnávací studie MeSH
- Názvy látek
- chromatin MeSH
- histony MeSH
- messenger RNA MeSH
- ribozomální DNA MeSH
Epigenetic modifications, such as acetylation, phosphorylation, methylation, ubiquitination, and ADP ribosylation, of the highly conserved core histones, H2A, H2B, H3, and H4, influence the genetic potential of DNA. The enormous regulatory potential of histone modification is illustrated in the vast array of epigenetic markers found throughout the genome. More than the other types of histone modification, acetylation and methylation of specific lysine residues on N-terminal histone tails are fundamental for the formation of chromatin domains, such as euchromatin, and facultative and constitutive heterochromatin. In addition, the modification of histones can cause a region of chromatin to undergo nuclear compartmentalization and, as such, specific epigenetic markers are non-randomly distributed within interphase nuclei. In this review, we summarize the principles behind epigenetic compartmentalization and the functional consequences of chromatin arrangement within interphase nuclei.
- MeSH
- acetylace MeSH
- buněčné jádro metabolismus ultrastruktura MeSH
- chromatin ultrastruktura MeSH
- chromozomální proteiny, nehistonové fyziologie MeSH
- epigeneze genetická MeSH
- exprese genu MeSH
- histony genetika metabolismus MeSH
- homolog proteinu s chromoboxem 5 MeSH
- inhibitory histondeacetylas MeSH
- interfáze MeSH
- lidé MeSH
- lidské chromozomy X metabolismus MeSH
- metylace MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- chromatin MeSH
- chromozomální proteiny, nehistonové MeSH
- histony MeSH
- homolog proteinu s chromoboxem 5 MeSH
- inhibitory histondeacetylas MeSH
Nuclear locations of the c-myc gene and its transcripts (c-myc (T)) have been investigated in relation to nuclear domains involved in RNA synthesis and processing. Transcription of the c-myc gene appears to be linked to the late G(1)- and preferentially to S-phases of the cell cycle. The c-myc gene and its transcripts were positioned non-randomly within the interphase nucleus; additionally, c-myc RNA signals accumulated at nucleoli. Using oligo-probes, designed to exon II and exon III of the c-myc gene, single c-myc (T) was preferentially observed in human carcinoma HT29 and A549 cells. Conversely, human embryonal teratocarcinoma NTERA cells were characterized by the presence of multiple c-myc RNA signals located in both the nucleoli and nucleoplasm. When accumulated at nucleoli, c-myc (T) occupied the periphery of this organelle, though not those associated with the cultivation surface. In HT29 cells, approximately 80% of c-myc (T) co-localized with the RNAP II positive regions, so-called transcription factories. However, in approximately 20% of the cells with c-myc transcripts, the c-myc (T) was released from the site of synthesis, and was not associated with either transcription factories or SC35 domains. In approximately 60% of nuclei with c-myc (T), these signals were located in close proximity to the SC35 regions, but promyelocytic leukaemia bodies were associated with c-myc (T) only in approximately 20% of the nuclei. Taken together, c-myc RNA signals were positioned in the most internal parts of the cell nuclei preferentially associated with the nucleoli. Specific nuclear and nucleolar positioning probably reflects the kinetics of c-myc RNA metabolism.
- MeSH
- buněčné jádro genetika metabolismus ultrastruktura MeSH
- buňky HT-29 MeSH
- exprese genu MeSH
- genetická transkripce MeSH
- geny myc * MeSH
- lidé MeSH
- lidské chromozomy, pár 8 MeSH
- messenger RNA metabolismus MeSH
- nádorové buňky kultivované MeSH
- protoonkogenní proteiny c-myc metabolismus MeSH
- RNA-polymerasa II metabolismus MeSH
- tkáňová distribuce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- messenger RNA MeSH
- MYC protein, human MeSH Prohlížeč
- protoonkogenní proteiny c-myc MeSH
- RNA-polymerasa II MeSH
The spatial arrangement of some genetic elements relative to chromosome territories and in parallel with the cell nucleus was investigated in human lymphocytes. The structure of the chromosome territories was studied in chromosomes containing regions (clusters) of highly expressed genes (HSA 9, 17) and those without such clusters (HSA 8, 13). In chromosomes containing highly expressed regions, the elements pertaining to these regions were found close to the centre of the nucleus on the inner sides of chromosome territories; those pertaining to regions with low expression were localized close to the nuclear membrane on the opposite sides of the territories. In chromosomes with generally low expression (HSA 8, 13), the elements investigated were found symmetrically distributed over the territories. Based on the investigations of the chromosome structure, the following conclusions are suggested: (1) Chromosome territories have a non-random internal 3D structure with defined average mutual positions between elements. For example, RARalpha, TP53 and Iso-q of HSA 17 are nearer to each other than they are to the HSA 17 centromere. (2) The structure of a chromosome territory reflects the number and chromosome location of clusters of highly expressed genes. (3) Chromosome territories behave to some extent as solid bodies: if the territory is found closer to the nuclear centre, the individual genetic elements of this chromosome are also found, on average, closer the centre of the nucleus. (4) The positions of centromeres are, on average, nearer to the fluorescence weight centre of the territory (FWCT) than to genes. (5) Active genes are not found near the centromeres of their own territory. A simple model of the structure of chromosome territory is proposed.
- MeSH
- buněčné jádro genetika MeSH
- centromera genetika MeSH
- euchromatin genetika MeSH
- geny MeSH
- heterochromatin genetika MeSH
- hybridizace in situ fluorescenční MeSH
- jaderný obal genetika MeSH
- kompartmentace buňky MeSH
- lidé MeSH
- lidské chromozomy, pár 17 ultrastruktura MeSH
- lidské chromozomy ultrastruktura MeSH
- lymfocyty diagnostické zobrazování MeSH
- metoda Monte Carlo MeSH
- modely genetické MeSH
- počítačová simulace MeSH
- počítačové zpracování obrazu MeSH
- ultrasonografie MeSH
- zobrazování trojrozměrné * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- euchromatin MeSH
- heterochromatin MeSH