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Results for “Chromatin Dynamics”

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At least 73 records · Page 4Linked to original sources
PubMed2004

Linking lipids to chromatin.

Dynamic regulation of chromatin structure is thought to be a prerequisite for nuclear functions that require accessibility to DNA such as replication, transcription and DNA repair. The phosphoinositide (PI) pathway is a second messenger signalling system regulated in response to a variety of extracellular (growth factors, differentiation signals) and intracellular (cell cycle progression, DNA damage) stimuli. The presence of a PI pathway in the nucleus together with the recent findings that specific nuclear proteins can interact with and are regulated by phosphoinositides suggest that changes in the nuclear phosphoinositide profile may have a direct role in modulating chromatin structure.

Chromatin↗
PubMed2026

Mixing chromatin fibers with different nucleosome repeat lengths changes dynamics of chromatin phase separation.

The eukaryotic genome is organized into chromatin at multiple lengths and timescales. Liquid-liquid phase separation has recently emerged as a mechanism for the dynamic compartmentalization of chromatin. However, it remains unclear how cells can locally alter phase separation behavior to condense, decondense, and segregate specific regions of their genome. Selective interactions between chromatin fibers with different nucleosome repeat lengths (NRLs), as well as their incorporation into existing condensates composed of different NRL chromatin fibers, may provide a pathway for such processes. Using fluorescence microscopy, we investigated how these mechanisms influence the formation, coalescence, and maturation of chromatin condensates. Our results show distinct NRL-dependent mixing behaviors of chromatin before and after condensate formation. 167 and 197 NRL fibers, known to fold into compact fibers by strong nucleosome stacking interactions, formed amorphous condensates. In contrast, 172 and 202 NRL fibers, which only allow for weak stacking, formed spherical condensates. When NRLs were mixed, amorphous condensates exhibited localized clustering of identical NRLs. In spherical condensates, however, both NRLs were homogeneously distributed, with a varying NRL ratio per condensate. In addition, incorporation of 167 NRLs into preexisting 172 NRL condensates resulted in a multiphase structure where 167 NRL fibers formed an outer layer. These findings present an intrinsic link between DNA sequence, nucleosome positioning, local chromatin configuration and multiscale phase separation behavior. More broadly, they contribute to a deeper understanding of the dynamic methods of genome organization employed by eukaryotic organisms.

chromatin↗
PubMed1999

Macronuclear chromatin structure dynamics in Colpoda inflata (Protista, Ciliophora) resting encystment.

The chromatin structure dynamics of the Colpoda inflata macronucleus have been investigated in relation to its functional condition, concerning chromatin body extrusion regulating activity. Samples of 2- and 25-day-old resting cysts derived from a standard culture, and of 1-year-old resting cysts derived from a senescent culture, were examined by means of histogram analysis performed on acquired optical microscopy images. Three groups of histograms were detected in each sample. Histogram classification, clustering and matching were assessed in order to obtain the mean histogram of each group. Comparative analysis of the mean histogram showed a similarity in the grey level range of 25-day- and 1-year-old cysts, unlike the wider grey level range found in 2-day-old cysts. Moreover, the respective mean histograms of the three cyst samples appeared rather similar in shape. All this implies that macronuclear chromatin structural features of 1-year-old cysts are common to both cyst standard cultures. The evaluation of the acquired images and their respective histograms evidenced a dynamic state of the macronuclear chromatin, appearing differently condensed in relation to the chromatin body extrusion regulating activity of the macronucleus. The coexistence of a chromatin-decondensed macronucleus with a pycnotic extrusion body suggests that chromatin unable to decondense, thus inactive, is extruded. This finding, along with the presence of chromatin structural features common to standard and senescent cyst populations, supports the occurrence of 'rejuvenated' cell lines from 1-year-old encysted senescent cells, a phenomenon which could be a result of accomplished macronuclear renewal.

Animals↗
PubMed1984

Chromatin assembly in Xenopus oocytes: in vivo studies.

We have followed the time course of chromatin assembly, DNA supercoiling, and transcription on a Xenopus 5S RNA gene clone injected into germinal vesicles of Xenopus oocytes. During the first 2 hr after DNA injection, there is a gradual enhancement in transcription that correlates with the increase in superhelical density of the DNA template; on the other hand, nucleosome assembly is already completed by 10-30 min after DNA injection. To probe further the DNA structure in the assembled minichromosomes, we injected enzymes and chemicals into the germinal vesicle. DNAase I and topoisomerase I injections reveal that the circular DNA has been assembled into two discrete and equally abundant types of chromatin: one type, which we call "dynamic" chromatin, is torsionally strained and is thus fully relaxed by those two enzymes. The other type, which we call "static" chromatin, still yields supercoiled DNA molecules after deproteinization. The dynamic chromatin is also relaxed by injection of novobiocin, and simultaneously, 5S RNA transcription is turned off. The results of our in vivo experiments suggest that the dynamic chromatin is the one that is transcriptionally active. We discuss the biological relevance of these findings.

Animals↗
PubMed2006

Micromanipulation studies of chromatin fibers in Xenopus egg extracts reveal ATP-dependent chromatin assembly dynamics.

We have studied assembly of chromatin using Xenopus egg extracts and single DNA molecules held at constant tension by using magnetic tweezers. In the absence of ATP, interphase extracts were able to assemble chromatin against DNA tensions of up to 3.5 piconewtons (pN). We observed force-induced disassembly and opening-closing fluctuations, indicating our experiments were in mechanochemical equilibrium. Roughly 50-nm (150-base pair) lengthening events dominated force-driven disassembly, suggesting that the assembled fibers are chiefly composed of nucleosomes. The ATP-depleted reaction was able to do mechanical work of 27 kcal/mol per 50 nm step, which provides an estimate of the free energy difference between core histone octamers on and off DNA. Addition of ATP led to highly dynamic behavior with time courses exhibiting processive runs of assembly and disassembly not observed in the ATP-depleted case. With ATP present, application of forces of 2 pN led to nearly complete fiber disassembly. Our study suggests that ATP hydrolysis plays a major role in nucleosome rearrangement and removal and that chromatin in vivo may be subject to highly dynamic assembly and disassembly processes that are modulated by DNA tension.

Adenosine Triphosphate↗
PubMed2003

Embryonic stem cell differentiation: a chromatin perspective.

Embryonic stem (ES) cells hold immense promise for the treatment of human degenerative disease. Because ES cells are pluripotent, they can be directed to differentiate into a number of alternative cell-types with potential therapeutic value. Such attempts at "rationally-directed ES cell differentiation" constitute attempts to recapitulate aspects of normal development in vitro. All differentiated cells retain identical DNA content, yet gene expression varies widely from cell-type to cell-type. Therefore, a potent epigenetic system has evolved to coordinate and maintain tissue-specific patterns of gene expression. Recent advances show that mechanisms that govern epigenetic regulation of gene expression are rooted in the details of chromatin dynamics. As embryonic cells differentiate, certain genes are activated while others are silenced. These activation and silencing events are exquisitely coordinated with the allocation of cell lineages. Remodeling of the chromatin of developmentally-regulated genes occurs in conjunction with lineage commitment. Oocytes, early embryos, and ES cells contain potent chromatin-remodeling activities, an observation that suggests that chromatin dynamics may be especially important for early lineage decisions. Chromatin dynamics are also involved in the differentiation of adult stem cells, where the assembly of specialized chromatin upon tissue-specific genes has been studied in fine detail. The next few years will likely yield striking advances in the understanding of stem cell differentiation and developmental biology from the perspective of chromatin dynamics.

Animals↗
PubMedDate not supplied

[Dynamics of chromatin position within the interphase nucleus].

In this article we attempt to analyze the relationship between the processes, which occur in the nucleus, and the dynamics of chromatin, as well as to classify the changes in the position of chromatin in the cell nucleus during the lifetime of the cell. The proposed concept integrates possible types of chromatin movement within the nucleus.

Animals↗
PubMed2003

Chromatin of endoreduplicated pavement cells has greater range of movement than that of diploid guard cells in Arabidopsis thaliana.

In the current model of chromatin organization in the interphase cell nucleus, chromosomes are organized into territories. Although constrained diffusion of chromatin in interphase cells has been confirmed in all cell types examined, little is known about chromatin dynamics in plant interphase cells. In this work, we measured for the first time interphase chromatin dynamics in plants using the green-fluorescent-protein-mediated chromatin-tagging system. Moreover, we compared the dynamics of diploid guard cells and endoreduplicated pavement cells. The movement of tagged loci in live seedlings shows constrained behavior in both types of nuclei. However, we found that the apparent confinement area for tagged loci in pavement cells is over 6 times larger than it is in guard cells. These findings suggest that chromatin is anchored to some component of the nucleus and that this might be responsible for the different dynamics of chromatin diffusion between diploid cells and endoreduplicated cells.

Arabidopsis↗
PubMed1995

Mechanism of protein access to specific DNA sequences in chromatin: a dynamic equilibrium model for gene regulation.

We present evidence for a mechanism by which regulatory proteins may gain access to their target DNA sequences in chromatin. In this model, nucleosomes are dynamic structures, transiently exposing stretches of their DNA. Regulatory proteins gain access to DNA target sites in the exposed state, and bind with an apparent dissociation constant equal to their dissociation constant for naked DNA divided by a position-dependent equilibrium constant for site exposure within the nucleosome. A sensitive assay, based on the kinetics of restriction digestion of sites within nucleosomes, reveals this dynamic behaviour and quantifies the equilibrium constants for site exposure. Our results have implications for many aspects of chromatin function. They offer new mechanisms for cooperativity (synergy) in regulatory protein binding and for active invasion of nucleosomes.

Base Sequence↗
PubMed1998

Chromatin-remodeling factors: machines that regulate?

Chromatin has shifted into the focus of attention as a key to understanding the regulation of nuclear processes such as transcription. Protein machines have been described that use the energy of ATP to render chromatin dynamic and hence active, but which may also be involved in chromatin assembly. The discovery of three different Drosophila nucleosome remodeling complexes that contain imitation switch (ISWI), an ATPase with a high degree of sequence conservation from yeast to human, points to a central function of this ATPase in chromatin dynamics.

Adenosine Triphosphatases↗
PubMed2005

How does the histone code work?

Patterns of histone post-translational modifications correlate with distinct chromosomal states that regulate access to DNA, leading to the histone-code hypothesis. However, it is not clear how modification of flexible histone tails leads to changes in nucleosome dynamics and, thus, chromatin structure. The recent discovery that, like the flexible histone tails, the structured globular domain of the nucleosome core particle is also extensively modified adds a new and exciting dimension to the histone-code hypothesis, and calls for the re-examination of current models for the epigenetic regulation of chromatin structure. Here, we review these findings and other recent studies that suggest the structured globular domain of the nucleosome core particle plays a key role regulating chromatin dynamics.

Acetylation↗
PubMed1986

The dynamics of chromatin carcinogen interactions in the human cell.

Human lung epithelioid cells were treated with Benzo (a) pyrene diol epoxide (anti) in order to establish the binding and removal of covalent adducts in chromosomal components. Isolating two different classes of mononucleosomes, it was found that their DNA contained different concentrations of B(a)PDE-DNA adducts, while in both these mononucleosomal preparations only histones H2A and H3 contained detectable amounts of the carcinogen. Further analysis showed that in the intact human cell the carcinogen-DNA adduct distribution is constantly changing as a function of differential accessibility and repair. These results emphasize the dynamics of chromatin-carcinogen modifications.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2026

Feeding the epigenome: EZH2 as a metabolic integrator of cell fate in development and cancer.

Epigenetic regulation is intimately linked to cellular metabolism, enabling environmental and nutritional cues to shape gene expression programs through dynamic modifications of chromatin structure. This metabolism-epigenetics interface is mediated, in part, by the dependence of chromatin-modifying enzymes on key metabolites, including S-adenosylmethionine (SAM), acetyl-CoA, UDP-GlcNAc, and α-ketoglutarate, which serve as substrates or cofactors for DNA and histone modifications. Among these regulators, EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), has emerged as a key mediator linking metabolic state to epigenetic regulation by translating metabolic inputs into changes in chromatin architecture and gene expression. EZH2 governs developmental cell fate through H3K27me3-mediated gene repression and is frequently dysregulated in cancer, where it promotes dedifferentiation, tumor progression, and metabolic reprogramming. Importantly, EZH2 activity is itself modulated by cellular metabolic status through posttranslational modifications, including phosphorylation, acetylation, methylation, ubiquitination, and O-GlcNAcylation, which influence its stability, catalytic activity, and chromatin-binding capacity. These modifications are responsive to nutrient availability and signaling pathways involving glucose, SAM, NAD+, and other metabolic intermediates. Consequently, disruption of this finely tuned regulatory network can contribute to developmental abnormalities, metabolic dysfunction, and oncogenesis. In this review, we examine the molecular mechanisms governing EZH2 regulation and discuss how metabolic control of EZH2 shapes chromatin dynamics, cell fate decisions, and disease pathogenesis. Elucidating how metabolic signals modulate EZH2 activity will advance our understanding of development and disease while uncovering potential therapeutic opportunities to target metabolism-driven epigenetic dysregulation.

Humans↗
PubMed2003

Dynamics of chromatin, proteins, and bodies within the cell nucleus.

A new and still evolving paradigm of a highly dynamic nucleus has emerged in recent years. This paradigm includes an inherently high turnover rate of histone and non-histone protein modifications, targeted turnover and/or displacement of 'stable' core histone proteins, constant flux of macromolecules through chromosomes and nuclear bodies, including transcription factors and co-activators, and an energy-dependent facilitation of nuclear-protein complex formation and disassembly. Also included are fast, local movements of chromosomes, together with slower but long-range movements of chromosomes and nuclear bodies.

Cell Nucleus↗
PubMed1998

Control of gene expression in Xenopus early development.

We examine the control of gene expression before and through the MBT in Xenopus laevis. The generalized repression of transcription that occurs before the midblastula transition (MBT) is regulated by a dynamic competition between chromatin and transcription complex assembly. Conditions favoring the access of basal factors (TBP) or transactivators can overcome this transcriptional repression. Changes in DNase I hypersensitivity patterns of the chromatin during early development show that it is more accessible to DNase I before the MBT (and by extension to other DNA interacting proteins) than after the MBT. We also show that at the level of genomic domains, organization of the chromatin matrix attachment sites is random before MBT. We propose that these three components, chromatin domain structure, DNA accessibility, and the transcription complex-chromatin dynamic competition, combine to regulate transcription in the embryo before and through the MBT.

Animals↗
PubMed2005

Nucleosome and chromatin fiber dynamics.

Chromosomal DNA is packaged into condensed nucleoprotein suprastructures, yet the DNA can be accessed as needed within this structural context. Recently, progress has been made concerning how the nucleosomal subunits of chromatin fibers are disassembled and reassembled in vitro and in vivo. At the level of the chromatin fiber, the conformational organization of condensed 30 nm secondary structures has been elucidated. A great deal of progress also has been made toward understanding how chromatin architectural proteins, such as MeCP2, MENT, polycomb and HP1alpha, assemble different specific types of secondary and tertiary chromatin structures. The emerging picture is that the inherent dynamics of nucleosomal assemblages at all structural levels are a key link between the condensed domains found in eukaryotic genomes and the functions that take place within them.

Animals↗
PubMed2004

Progress and challenges in profiling the dynamics of chromatin and transcription factor binding with DNA microarrays.

ChIP-chip, or chromatin immunoprecipitation followed by DNA microarray analysis, has proven to be an efficient means of mapping protein-genome interactions. Recent experiments using this tool are beginning to reveal the complex dynamics of transcription factor binding and chromatin organization, and how these processes interact with each other to generate a cellular response to environmental and developmental cues. Data derived from this approach, particularly data involving chromatin components and histone modifications, might be affected by assumptions underlying the procedure, and the data might be made more useful by adoption of standardized whole-genome microarray platforms.

Animals↗