Telomeres are specialized chromatin structures that are situated at the end of linear chromosomes and play an important role in cell senescence and immortalization. Here, we investigated whether changes in histone signature influence the nuclear arrangement and positioning of telomeres. Analysis of mouse embryonic fibroblasts revealed that telomeres were organized into specific clusters that partially associated with centromeric clusters. This nuclear arrangement was influenced by deficiency of the histone methyltransferase SUV39h, LMNA deficiency, and the histone deacetylase inhibitor Trichostatin A (TSA). Similarly, nuclear radial distributions of telomeric clusters were preferentially influenced by TSA, which caused relocation of telomeres closer to the nuclear center. Telomeres also co-localized with promyelocytic leukemia bodies (PML). This association was increased by SUV39h deficiency and decreased by LMNA deficiency. These differences could be explained by differing levels of the telomerase subunit, TERT, in SUV39h- and LMNA-deficient fibroblasts. Taken together, our data show that SUV39h and A-type lamins likely play a key role in telomere maintenance and telomere nuclear architecture.

• MeSH
• DNA vazebné proteiny metabolismus   MeSH
• epigeneze genetická MeSH
• fibroblasty metabolismus   MeSH
• genová přestavba MeSH
• intranukleární inkluzní tělíska metabolismus   MeSH
• lamin typ A metabolismus   MeSH
• lidé MeSH
• methyltransferasy metabolismus   MeSH
• myši MeSH
• protein TRF1 metabolismus   MeSH
• průtoková cytometrie MeSH
• rap1 proteiny vázající GTP metabolismus   MeSH
• represorové proteiny metabolismus   MeSH
• telomerasa metabolismus   MeSH
• telomery genetika   metabolismus   MeSH
• transport proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

Epigenetic marks are important factors regulating the pluripotency and differentiation of human embryonic stem cells (hESCs). In this study, we analyzed H3K9 acetylation, an epigenetic mark associated with transcriptionally active chromatin, during endoderm-like differentiation of hESCs. ChIP-on-chip analysis revealed that differentiation results in a genome-wide decrease in promoter H3K9 acetylation. Among the 24,659 promoters analyzed, only 117 are likely to be involved in pluripotency, while 25 acetylated promoters are likely to be responsible for endoderm-like differentiation. In pluripotent hESCs, the chromosomes with the highest absolute levels of H3K9 acetylation are chromosomes 1, 6, 2, 17, 11, and 12 (listed in order of decreasing acetylation). Chromosomes 17, 19, 11, 20, 22, and 12 are the most prone to differentiation-related changes (both increased acetylation and deacetylation). When chromosome size (in Mb) was accounted for, the highest H3K9 acetylation levels were found on chromosome 19, 17, 6, 12, 11, and 1, and the greatest differentiation-associated decreases in H3K9 acetylation occurred on chromosomes 19, 17, 11, 12, 16, and 1. The gene density and size of individual chromosomes were strongly correlated with the levels of H3K9 acetylation. Our analyses point to chromosomes 11, 12, 17, and 19 as being critical for hESC pluripotency and endoderm-like differentiation. J. Cell. Physiol. 219: 677-687, 2009. (c) 2009 Wiley-Liss, Inc.

• MeSH
• acetylace MeSH
• buněčná diferenciace fyziologie   genetika   MeSH
• buněčné linie MeSH
• chromatinová imunoprecipitace MeSH
• embryonální kmenové buňky cytologie   metabolismus   MeSH
• epigeneze genetická MeSH
• financování organizované MeSH
• genom lidský MeSH
• histony genetika   chemie   metabolismus   MeSH
• lidé MeSH
• lidské chromozomy genetika   metabolismus   MeSH
• pluripotentní kmenové buňky cytologie   metabolismus   MeSH
• promotorové oblasti (genetika) MeSH
• Check Tag
• lidé MeSH

The nuclear arrangement of promyelocytic leukaemia nuclear bodies (PML NBs) was studied in vitro after the cell treatment by clinically used agents such as all-trans retinoic acid (RA) in human leukaemia and cytostatics or gamma radiation in multiple myeloma cells. In addition, the influence of phorbol ester (PMA) on PML NBs formation was analyzed. A reduced number of PML bodies, which led to relocation of PML NBs closer to the nuclear interior, mostly accompanied RA- and PMA-induced differentiation. Centrally located PML NBs were associated with transcriptional protein RNAP II and SC35 regions, which support importance of PML NBs in RNA processing that mostly proceeds within the nuclear interior. Conversely, the quantity of PML NBs was increased after cytostatic treatment, which caused re-distribution of PML NBs closer to the nuclear envelope. Here we showed correlations between the number of PML NBs and average Centre-to-PML distances. Moreover, a number of cells in S phase, especially during differentiation, influenced number of PML NBs. Studying the proteins involved in PML compartment, such as c-MYC, cell-type specific association of c-MYC and the PML NBs was observed in selected leukaemic cells undergoing differentiation, which was accompanied by c-MYC down-regulation.

• MeSH
• akutní promyelocytární leukemie patologie   MeSH
• buněčná diferenciace účinky léků   MeSH
• buněčné jádro patologie   MeSH
• buněčný cyklus fyziologie   MeSH
• buňky K562 patologie   účinky léků   účinky záření   MeSH
• HL-60 buňky patologie   účinky léků   účinky záření   MeSH
• intranukleární inkluzní tělíska patologie   účinky léků   účinky záření   MeSH
• lidé MeSH
• melfalan farmakologie   MeSH
• mnohočetný myelom patologie   MeSH
• nádorové buněčné linie MeSH
• průtoková cytometrie MeSH
• tetradekanoylforbolacetát farmakologie   MeSH
• tretinoin farmakologie   MeSH
• U937 buňky patologie   MeSH
• záření gama MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH