remodelace chromatinu Dotaz Zobrazit nápovědu
This Special Issue highlights the advantages of using combined approaches to explore chromatin molecular complexes [...].
- MeSH
- chromatin * genetika MeSH
- genom * MeSH
- restrukturace chromatinu MeSH
- Publikační typ
- úvodníky MeSH
Nuclear phosphoinositides are recognized as regulators of many nuclear processes including chromatin remodeling, splicing, transcription, DNA repair and epigenetics. These processes are spatially organized in different nuclear compartments. Phase separation is involved in the formation of various nuclear compartments and molecular condensates separated from surrounding environment. The surface of such structures spatiotemporally coordinates formation of protein complexes. PI(4,5)P2 (PIP2) integration into phase-separated structures might provide an additional step in their spatial diversification by attracting certain proteins with affinity to PIP2. Our laboratory has recently identified novel membrane-free PIP2-containing structures, so called Nuclear Lipid Islets (NLIs). We provide an evidence that these structures are evolutionary conserved in different organisms. We hypothesize that NLIs serve as a scaffolding platform which facilitates the formation of transcription factories, thus participating in the formation of nuclear architecture competent for transcription. In this review we speculate on a possible role of NLIs in the integration of various processes linked to RNAPII transcription, chromatin remodeling, actin-myosin interaction, alternative splicing and lamin structures.
Cells belonging to the germ lineage segregate physically and molecularly from their somatic neighbors during embryogenesis. While germ line-specific chromatin modifications have been identified at later stages in the Caenorhabditis elegans nematode, none have been found in the single P4 germ line founder cell that arises at the beginning of gastrulation. Using light and electron microscopy, we now report that the chromatin organization in the germ line founder cell of the early C. elegans embryo is distinct from that in the neighboring somatic cells. This unique organization is characterized by a greater chromatin compaction and an expansion of the interchromatin compartment. The ultrastructure of individual chromatin domains does not differ between germ line and somatic cells, pointing to a specific organization mainly at the level of the whole nucleus. We show that this higher order reorganization of chromatin is not a consequence of the P4 nucleus being smaller than somatic nuclei or having initiated mitosis. Imaging of living embryos expressing fluorescent markers for both chromatin and P granules revealed that the appearance of a distinct chromatin organization in the P4 cell occurs approximately 10 min after its birth and coincides with the aggregation of P granules around the nucleus, suggesting a possible link between these two events. The higher order reorganization of chromatin that is reported here occurs during the establishment of definitive germ cell identity. The changes we have observed could therefore be a prerequisite for the programming of chromatin totipotency.
- MeSH
- Caenorhabditis elegans embryologie ultrastruktura MeSH
- chromatin metabolismus ultrastruktura MeSH
- embryo nesavčí metabolismus ultrastruktura MeSH
- restrukturace chromatinu fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
SUMOylation is a post-translational modification that positively regulates monoallelic expression of the trypanosome variant surface glycoprotein (VSG). The presence of a highly SUMOylated focus associated with the nuclear body, where the VSG gene is transcribed, further suggests an important role of SUMOylation in regulating VSG expression. Here, we show that SNF2PH, a SUMOylated plant homeodomain (PH)-transcription factor, is upregulated in the bloodstream form of the parasite and enriched at the active VSG telomere. SUMOylation promotes the recruitment of SNF2PH to the VSG promoter, where it is required to maintain RNA polymerase I and thus to regulate VSG transcript levels. Further, ectopic overexpression of SNF2PH in insect forms, but not of a mutant lacking the PH domain, induces the expression of bloodstream stage-specific surface proteins. These data suggest that SNF2PH SUMOylation positively regulates VSG monoallelic transcription, while the PH domain is required for the expression of bloodstream-specific surface proteins. Thus, SNF2PH functions as a positive activator, linking expression of infective form surface proteins and VSG regulation, thereby acting as a major regulator of pathogenicity.
- MeSH
- epigeneze genetická MeSH
- glykoproteiny genetika metabolismus MeSH
- protozoální proteiny genetika metabolismus MeSH
- restrukturace chromatinu MeSH
- RNA-polymerasa I metabolismus MeSH
- sumoylace * MeSH
- transkripční faktory genetika metabolismus MeSH
- Trypanosoma brucei brucei genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Smarca5, an ATPase of the ISWI class of chromatin remodelers, is a key regulator of chromatin structure, cell cycle and DNA repair. Smarca5 is deregulated in leukemia and breast, lung and gastric cancers. However, its role in oncogenesis is not well understood. Chromatin remodelers often play dosage-dependent roles in cancer. We therefore investigated the epigenomic and phenotypic impact of controlled stepwise attenuation of Smarca5 function in the context of primary cell transformation, a process relevant to tumor formation. Upon conditional single- or double-allele Smarca5 deletion, the cells underwent both accelerated growth arrest and senescence entry and displayed gradually increased sensitivity to genotoxic insults. These phenotypic characteristics were explained by specific remodeling of the chromatin structure and the transcriptome in primary cells prior to the immortalization onset. These molecular programs implicated Smarca5 requirement in DNA damage repair, telomere maintenance, cell cycle progression and in restricting apoptosis and cellular senescence. Consistent with the molecular programs, we demonstrate for the first time that Smarca5-deficient primary cells exhibit dramatically decreased capacity to bypass senescence and immortalize, an indispensable step during cell transformation and cancer development. Thus, Smarca5 plays a crucial role in key homeostatic processes and sustains cancer-promoting molecular programs and cellular phenotypes.
Chromatin Assembly Factor 1 (CAF-1) is a major nucleosome assembly complex which functions particularly during DNA replication and repair. Here we studied how the nucleosome landscape changes in a CAF-1 mutant in the model plant Arabidopsis thaliana. Globally, most nucleosomes were not affected by loss of CAF-1, indicating the presence of efficient alternative nucleosome assemblers. Nucleosomes that we found depleted in the CAF-1 mutant were enriched in non-transcribed regions, consistent with the notion that CAF-1-independent nucleosome assembly can compensate for loss of CAF-1 mainly in transcribed regions. Depleted nucleosomes were particularly enriched in proximal promoters, suggesting that CAF-1-independent nucleosome assembly mechanisms are often not efficient upstream of transcription start sites. Genes related to plant defense were particularly prone to lose nucleosomes in their promoters upon CAF-1 depletion. Reduced nucleosome occupancy at promoters of many defense-related genes is associated with a primed gene expression state that may considerably increase plant fitness by facilitating plant defense. Together, our results establish that the nucleosome landscape in Arabidopsis is surprisingly robust even in the absence of the dedicated nucleosome assembly machinery CAF-1 and that CAF-1-independent nucleosome assembly mechanisms are less efficient in particular genome regions.
- MeSH
- Arabidopsis genetika imunologie metabolismus MeSH
- chromatin genetika MeSH
- faktor 1 pro uspořádání chromatinu genetika metabolismus MeSH
- imunita rostlin genetika MeSH
- mutace MeSH
- nukleozomy genetika metabolismus MeSH
- oprava DNA genetika MeSH
- počátek transkripce MeSH
- promotorové oblasti (genetika) genetika MeSH
- replikace DNA genetika MeSH
- restrukturace chromatinu genetika MeSH
- sekvenční analýza DNA MeSH
- Publikační typ
- časopisecké články MeSH
Significant advances in chromosome preparation and other techniques have greatly increased the potential of plant cytogenetics in recent years. Increase in longitudinal resolution using DNA extended fibers as well as new developments in imaging and signal amplification technologies have enhanced the ability of FISH to detect small gene targets. The combination of fluorescence in situ hybridization with immunocytochemistry allows the investigation of cell events, chromosomal rearrangements and chromatin features typical for plant nuclei. Chromosome manipulation techniques using microdissection and flow sorting have accelerated the analysis of complex plant genomes. Together, the different cytogenetic approaches are invaluable for the unravelling of detailed structures of plant chromosomes, which are of utmost importance for the study of genome properties, DNA replication and gene regulation. In this technical review, different cytogenetic approaches are discussed for the analysis of plant chromosomes, with a focus on mitotic chromosomes.
IFN-γ is a pleiotropic cytokine crucial for both innate and adaptive immunity, which also plays a critical role in immunological surveillance of cancer. Genetic defects or gene silencing in the IFN-γ signal transduction pathways as well as in the expression of IFN-γ-regulated genes represent frequent mechanisms by which tumour cells can escape from immune responses. Epigenetic control of the IFN-γ signalling pathway activation associated with epigenetic changes in the corresponding regulatory gene regions, such as chromatin remodelling, histone acetylation and methylation, and DNA demethylation is frequently dysregulated in tumour cells. Epigenetic silencing of the IFN-γ regulatory pathway components, as well as of the IFN-γ-regulated genes crucial for tumour cell recognition or induction of anti-tumour immune responses, has been documented in various cancer models. Expression of both IFN-γ signalling pathway components and selected IFN-γ-regulated genes can be influenced by epigenetic modifiers, namely DNA methyltransferase and histone deacetylase inhibitors. These agents thus can mimic, restore, or boost the immunomodulatory effects of IFN-γ in tumour cells, which can contribute to their anti-tumour therapeutic efficacies and justifies their potential use in combined epigenetic therapy with immunotherapeutic approaches.
Nucleoli are the site of ribosomal RNA production and subunit assembly. In contrast to active nucleoli in somatic cells, where three basic sub-compartments can be observed, mammalian oocytes and early embryos contain atypical nucleoli termed "nucleolus-like bodies" or "nucleolus precursor bodies", respectively. Unlike their somatic counterparts, these structures are composed of dense homogenous fibrillar material and exhibit no polymerase activity. Irrespective of these unusual properties, they have been shown to be absolutely essential for embryonic development, as their microsurgical removal results in developmental arrest. Historically, nucleolus-like and nucleolus precursor bodies have been perceived as passive storage sites of nucleolar material, which is gradually utilized by embryos to construct fully functional nucleoli once they have activated their genome and have started to produce ribosomes. For decades, researchers have been trying to elucidate the composition of these organelles and provide the evidence for their repository role. However, only recently has it become clear that the function of these atypical nucleoli is altogether different, and rather than being involved in ribosome biogenesis, they participate in parental chromatin remodeling, and strikingly, the artificial introduction of a single NPB component is sufficient to rescue the developmental arrest elicited by the NPB removal. In this review, we will describe and summarize the experiments that led to the change in our understanding of these unique structures.
- MeSH
- buněčné jadérko genetika metabolismus MeSH
- chromatin genetika metabolismus MeSH
- embryonální vývoj genetika MeSH
- lidé MeSH
- restrukturace chromatinu * MeSH
- ribozomy genetika metabolismus MeSH
- zárodečné buňky metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
